Ten of the 11 major S&P sectors were lower, with a 2.2% decline in financials weighing the most on the S&P 500. Financial stocks tend to lag when the economic outlook darkens.
Technology and healthcare, the best performing sectors this year, were the only two in the positive territory.
"There is concern that perhaps we had gotten ahead of ourselves a little bit over the last couple of weeks," said Art Hogan, chief market strategist at National Securities in New York.
"Things are just going to stagnate here a bit as we consider how long it will actually take to get back in business and what kind of activity we see in front of us."
The battered S&P 1500 airlines index declined 4.6%, while cruise operators Carnival Corp and Norwegian Cruise Line Holdings Ltd fell 3.3% and 6.5%, respectively.
Marriott International Inc shed 6.1% after the hotel operator's quarterly profit fell short of already drastically lowered expectations as bookings plunged.
The Nasdaq, however, edged higher as gains for tech-related stocks helped it build on a rally last week where it recovered all its 2020 losses on hopes of a pickup in business activity.
The tech-heavy index is now just 7% below its February record high, but analysts have warned of another selloff as macroeconomic data gets worse, foreshadowing a deep and lasting global recession.
After financial markets began pricing in negative US interest rates for the first time ever last week, all eyes will be on Federal Reserve Chair Jerome Powell's outlook on the economy at a webcast event on Wednesday.
At 11:00 a.m. ET, the Dow Jones Industrial Average was down 217.25 points, or 0.89%, at 24,114.07, the S&P 500 was down 16.49 points, or 0.56%, at 2,913.31.
The Nasdaq Composite was up 6.24 points, or 0.07%, at 9,127.56.
Drug distributor Cardinal Health Inc jumped 5.2% as the pandemic drove a surge in third-quarter sales, which topped market estimates.
Athletic apparel maker Under Armour Inc slumped 11.1% after it forecast a 50% to 60% drop in second-quarter revenue, while General Mills Inc rose 0.9% after it said it expects to surpass its own expectations for fiscal 2020 organic sales.
Declining issues outnumbered advancers for a 3.21-to-1 ratio on the NYSE and a 1.70-to-1 ratio on the Nasdaq.
The S&P index recorded 12 new 52-week highs and one new low, while the Nasdaq recorded 65 new highs and five new lows.