The Dow Jones Industrial Average decreased 85.19 points, or 0.31 percent, to 27,692.88. The S&P 500 fell 14.93 points, or 0.44 percent, to 3,374.85. The Nasdaq Composite Index was down 64.38 points, or 0.57 percent, to 11,146.46.
All the 11 primary S&P 500 sectors ended lower, with real estate down 2.02 percent, leading the losses.
On the corporate side, Target shares soared 12.65 percent after the U.S. retail giant reported quarterly results topping Wall Street's expectations.
Apple hit a market cap of 2 trillion U.S. dollars earlier in the session to become the first publicly traded U.S. company to reach the milestone. However, its market cap fell below the 2-trillion-dollar mark at the close as the shares eked out a modest gain of 0.13 percent, well off intraday highs.
Meanwhile, U.S.-listed Chinese companies traded mostly lower, with seven of the top 10 stocks by weight in the S&P U.S. Listed China 50 index ending the day on a downbeat note.
The U.S. central bank on Wednesday released the minutes from its July meeting.
"Members agreed that the ongoing public health crisis would weigh heavily on economic activity, employment, and inflation in the near term and was posing considerable risks to the economic outlook over the medium term," said the minutes.
The Fed slashed interest rates to near zero earlier this year in an effort to support the economy amid the pandemic shock.
As of Wednesday afternoon, the United States has reported more than 5.5 million COVID-19 cases and over 172,000 deaths, according to a tally by Johns Hopkins University.
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