"If you think the current level of market volatility is high, it will get a lot worse if Britain votes for Brexit next week. It's not a panic yet but there are clearly signs of stress in the (City of London) and the wider markets. Traders are getting nervous and for good reason," Andrew Edwards, CEO of spread better ETX Capital, said in a morning note.
"Several recent polls suggest Britain will head for the exits - the latest survey gives leave a 7-point lead."
U.S. stocks closed lower Tuesday, amid declines in oil prices. On Wednesday morning, European stocks traded higher after a rocky start and in Asia, Chinese markets led gains in a mixed session, shrugging off a decision by stock index provider MSCI on Tuesday to delay inclusion of mainland-traded Chinese A shares in its key emerging market index.
Back in the U.S., traders monitored fresh data with May PPI and an Empire State survey both coming in better than expected.
The producer price index rose a slightly more-than-expected 0.4 percent in May, following a 0.2 percent rise the prior month, the Labor Department said. In the 12 months through May, PPI fell 0.1 percent after being unchanged in April.
The core PPI that excludes food, energy and trade services fell 0.1 percent last month after rising 0.3 percent in April, for a 0.8 percent rise in the 12 months through May.
The June 2016 Empire State Manufacturing Survey rose to 6.0 from a negative 9 print last month.
Industrial production numbers showed a decline of 0.4 percent in May and April's figure was revised lower to show a 0.6 percent increase versus the previously reported 0.7 percent. May capacity utilization edged lower from the prior month to 74.9 percent.
Fed Chair Janet Yellen's press briefing will take place at 2:30 p.m. ET and TIC data will be released at 4 p.m. ET.
—CNBC's Patti Domm and Saheli Roy Choudhury contributed to this article.