The Nasdaq composite underperformed, ending about 0.4 percent lower as biotech stocks and semiconductors declined.
Health care closed about 0.4 percent higher. The sector briefly rallied more than 1 percent to lead S&P 500 advancers, helped by gains of more than 5.5 percent in Allergan. The firm confirmed that it has been approached by Pfizer and is in talks regarding a potential deal. Shares of both companies were briefly halted. Pfizer closed down nearly 2 percent.
The rate-sensitive utilities sector was the greatest decliner in the S&P, while financials was the second-greatest laggard after leading Wednesday's post-Fed statement rally.
"Basically we're hanging on to the 200 points from yesterday," said Michael Farr, president and CEO of Farr, Miller & Washington.
"I don't think the market expects the Fed to move at all," he said, noting the statement was "pure wordsmithing and not material in terms of action."
The Federal Reserve issued a post-meeting statement Wednesday that was more hawkish than many expected. In the statement, the central bank downplayed September's concerns about impact from global growth and specifically noted it will be looking for progress in employment and labor when considering whether to raise rates at its December meeting.
The specific mention of the Fed's next meeting immediately triggered a significant move up in market expectations for a rate hike this year.
Bond yields held higher after rising Wednesday. The 10-year yield was 2.17 percent and the 2-year yield 0.71 percent.
The U.S. dollar traded half a percent lower against major world currencies, with the euro at $1.09 and the yen at 121.08 yen against the dollar.
Many market analysts do not see enough economic support for the Fed to raise rates later this year.
"All data in the last three months shows some slowing," said James Meyer, chief investment officer at Tower Bridge Advisors. "All they did yesterday was set the table, gave themselves the option (to hike in December)."
Read MoreFed tells markets to wake up, a rate hike could be coming
"As long as we have this disagreement in the market I think it's going to be very difficult for stocks to reach new highs," said Chuck Self, chief investment officer of iSectors. "We're going to be in this trading range for the next few months."
The three major averages are up nearly 9 percent or more for October so far, on track for their best month since October 2011.
"The dynamic has shifted from August and September," said Adam Sarhan, CEO of Sarhan Capital. "You're seeing weakness being bought instead of weakness being sold and that's a big shift."