The Nasdaq composite ended a touch lower after an intraday attempt to recover a 1 percent dip and trade higher. Apple closed just below the flatline after falling more than 1 percent.
Biotech stocks bucked the overall decline to close higher. Health care was the only advancer in the S&P 500 and the iShares Nasdaq Biotechnology ETF (IBB) gained nearly 2 percent.
IBB plunged 2.2 percent Monday and attempted to recover most of those losses Tuesday amid the conclusion of the American Society of Hematology (ASH) Annual Meeting.
"I think a combination of rebounding from yesterday's overreaction and positive news from Alexion," said Paul Yook, portfolio manager at BioShares Funds. The U.S. Food and Drug Administration on Tuesday approved Alexion Pharmaceutical's treatment for a rare and potentially fatal genetic disorder.
"I think we're starting to see more sentiment that some of these drugs are starting to get approved," said Mike Bailey, director of research and chair at FBB Capital Partners.
The Dow Jones industrial average ended about 160 points lower after earlier falling as much as 245 points, with Boeing and Goldman Sachs the greatest weights on the index.
U.S. stocks closed lower Monday, weighed by a sharp decline in energy stocks as oil plunged to a near-seven-year low after OPEC failed on Friday to agree on a production curb to stem sliding prices. Analysts also noted some pressure from a stronger U.S. dollar.
The dollar index traded slightly lower, while the euro held higher just below $1.09. The yen traded near 122.96 yen against the greenback in the close.
"We had that issue (of oil declines) yesterday and I think that's the issue today. Certainly that's contributed to the last leg lower (in stock index futures). The China trade data has spooked things," said FBN Securities Chief Market Strategist Jeremy Klein.
He noted "few people want to take risk" in a relatively quiet week for U.S. data ahead of the Federal Reserve's meeting next week, when the central bank could raise rates for the first time in nearly a decade. "No one wants to stand in front of any selling after what has been a rocky year," he said.
Bank of America Merrill Lynch Head of U.S. Equity Savita Subramanian said Tuesday the firm's price target for the S&P 500 next year is 2,200. "I think next year is going to be a great year for value investing," she said at the firm's 2016 outlook.
The firm expects S&P 500 earnings growth of 5 percent next year, as the roughly 60 percent negative drag from energy earnings this year diminishes to flat.
Read MoreBofA says S&P 500 will hit 3,500 on this date
Chinese trade data released overnight showed exports declined for the fifth-straight month and imports down a record 13 months, according to StreetAccount. However, the decline in imports was less than expected and slowed from last month. The drop in both imports and exports add to concerns about global growth and a tepid domestic demand-driven recovery.
Reuters noted that China crude oil imports for the first 11 months of the year rose 8.7 percent to 6.61 million barrels per day, with November crude imports growing 7.6 percent from the same month a year ago. The news helped oil briefly attempt gains in early morning trade.
Asian stocks sold off sharply, with the Shanghai composite the worst performer with a roughly 1.9 percent decline.
Dow futures fell 200 points in pre-market trade, following declines in European stocks. The German DAX, France CAC 40 and STOXX Europe 600 each ended more than 1.5 percent lower.
The Chinese trade data and low oil prices added to concerns about global growth, Ablin said. "I think investors worry, we don't know what the bottom in oil was, now that we're dropping below $40."
The commodity-sensitive materials sector and industrials led nearly all S&P 500 sectors lower. Energy was the third-greatest decliner but ended off session lows. The Alerian Master Limited Partnership ETF (AMLP) closed about 3 percent higher after falling nearly 7 percent Monday.
The S&P 500 briefly joined the Dow in negative territory for 2015 in intraday trade as energy weighed. The Energy SPDR (XLE) still posted five-straight days of losses for the first time since a six-day losing streak in late August.
In U.S. economic news, the Job Openings and Labor Turnover Survey showed 5.383 million openings in October, while the September figure was revised slightly higher to 5.534 million. The quits rate held steady from September at 1.9 percent.
The National Federation of Independent Business said on Tuesday its Small Business Optimism Index fell 1.3 points to 94.8 in November. While the index is below its 42-year average, NFIB said the print continued to signal the economy was "plodding" along.
"I don't think this has been a data story (other) than the market being more convinced the Fed is moving," said Joe Lavorgna, chief U.S. economist and managing director at Deutsche Bank Securities.
"When investors start to see weak equities and oil hitting new lows, you see people getting a little nervous, taking profits going into year-end," he said.
Treasury yields held little changed, with the 2-year yield a touch higher at 0.94 percent and the 10-year yield flat at 2.22 percent. The Treasury Department auctioned $24 billion of 3-year notes at a high yield of 1.255 percent.
Qualcomm closed down 5.6 percent after European Union antitrust regulators charged the firm with abusing its market power to thwart rivals, putting the world's number one mobile chipset maker at risk of a hefty fine, Reuters said. The chipmaker also said the Taiwan Fair Trade Commission opened an investigation into its patent licensing deals.
Chipotle said a Boston College statement about at least 80 students falling ill after eating at Chipotle Mexican Grill appeared to be an isolated incident. Shares of Chipotle closed down 1.7 percent, nearly 21 percent lower year-to-date.
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The Dow Jones industrial average closed down 162.51 points, or 0.92 percent, at 17,568.00, with Exxon Mobil leading decliners and Nike and McDonald's the only advancers.
The S&P 500 closed down 13.48 points, or 0.65 percent, at 2,063.59, with materials leading nine sectors lower and health care the only advancer.
The Nasdaq composite closed down 3.57 points, or 0.07 percent, at 5,098.24.
The CBOE Volatility Index (VIX), widely considered the best gauge of fear in the market, climbed above 17.
About two stocks declined for every advancer on the New York Stock Exchange, with an exchange volume of 971 million and a composite volume of nearly 4.2 billion in the close.
Gold futures for February delivery settled 10 cents higher at $1,075.30 an ounce.
—Reuters contributed to this report.
On tap this week:
7 a.m.: Mortgage Applications
10 a.m.: Wholesale trade
10:30 a.m.: Oil inventories
1 p.m.: 10-year note auction
8:30 a.m. Initial claims; import prices
10:30 a.m.: Natural gas inventories
1 p.m.: 30-year bond auction
2 p.m.: Federal budget
4:30 p.m.: Fed balance sheet/money supply
8:30 a.m. Retail sales; PPI
10 a.m.: Consumer sentiment; business inventories
1 p.m.: Rig count
*Planner subject to change.
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