The Dow Jones Industrial Average fell for a second consecutive session as oil prices slid, dragging down energy shares.
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The blue-chip index has wobbled since oil fell into a bear market on Tuesday, renewing concerns among some analysts that there could be a more severe pullback in commodity prices.
Energy stocks, the worst-performing sector in the S&P 500 this year, have fallen more than the other 10 groups in the broad index so far this week.
Still, many investors and analysts say they remain cautiously optimistic about the outlook for the U.S. stock market.
Strong earnings have supported stock indexes this year, and valuations -- which are trading at higher-than-average levels -- haven't risen to excessive levels, said Tom Siomades, head of the investment consulting group of Hartford Funds.
"We're not at the point where we think we need to cash out from the U.S. yet," Mr. Siomades said. "Global growth hasn't been great, but it's been OK, and that's helping us hang in there."
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The Dow industrials fell 57.11 points, or 0.3%, to 21410.03, with declines in Chevron and Exxon Mobil shaving off 20 points from the index.
The S&P 500 lost 1.42 point, or less than 0.1%, to 2435.61 and the Nasdaq Composite added 45.92 points, or 0.7%, to 6233.95, boosted by gains in the shares of health-related companies.
Health-care stocks in the S&P 500 rose 1.2%, with Regeneron Pharmaceuticals -- the second-biggest gainer in the S&P 500 on Tuesday -- extending its rally to add $26.69, or 5.4%, to $522.02 Wednesday. The sector, the worst-performing group in the S&P 500 in 2016, has rebounded this year in part as investors have bought shares of biotechnology companies.
U.S. crude for August delivery fell 2.3% to $42.53 a barrel -- its lowest settlement since August -- after government data showed U.S. oil output continuing to rise last week . Energy shares in the S&P 500 fell 1.6%.
Transocean shares declined 41 cents, or 5%, to 7.79 -- the lowest close on record.
Government bonds edged lower, with the yield on the 10-year U.S. Treasury note rising to 2.156% from 2.153% Tuesday. Yields rise as bond prices fall.
Elsewhere, the Stoxx Europe 600 slipped 0.2% but closed off its worst levels of the day.
Stocks across the Asia-Pacific region mostly fell amid losses in energy companies and banks, with the Nikkei Stock Average dropping 0.5% and Hong Kong's Hang Seng Index falling 0.6%.
Mainland China markets inched higher, however, after MSCI Inc. said it would include China A-shares in its emerging-markets index, meaning funds that track it will automatically allocate money into China.
"For global investors, while the inclusion will not trigger an immediate and wholesale change in their asset allocation, it will put Chinese equities on the map," Aidan Yao, economist at AXA Investment Managers, said in a note.
The Shanghai Composite Index added 0.5%.
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(END) Dow Jones Newswires
June 21, 2017 17:13 ET (21:13 GMT)