With one trading day left, the S&P 500 was set to end the year more than 27% higher, with the Nasdaq up about 23% and the Dow's annual rise just shy of 20%. Each of Wall Street's main indexes was poised for its sharpest three-year surge since 1997-99.
The Dow Jones Industrial Average fell 90.55 points, or 0.25%, to 36,398.08, the S&P 500 lost 14.33 points, or 0.30%, to 4,778.73 and the Nasdaq Composite dropped 24.65 points, or 0.16%, to 15,741.56.
Four of the 11 major S&P 500 sector indexes traded higher, led by the real estate sector.
Investors cheered a U.S. Labor Department report that the number of Americans filing for new unemployment claims dropped to a seasonally adjusted 198,000 in the week leading up to Christmas, from a revised 206,000 a week earlier. Economists polled by Reuters had forecast weekly applications would rise to 208,000.
In other strong U.S. data, the Chicago purchasing managers' index (PMI) delivered a print of 63.1, a monthly increase of 1.3 points and 1.1 points above consensus.
A PMI number over 50 signifies expanded activity over the previous month.
Equities have rallied recently on some of the thinnest trading volumes that U.S. stock exchanges have seen due to the holidays. Investors were encouraged by growing evidence that the Omicron variant causes less-severe infections of COVID-19 than the Delta strain.
On Wednesday, top U.S. infectious disease adviser Dr. Anthony Fauci said the surge in cases of the Omicron variant should peak by the end of January.
"The strong manufacturer data out of Chicago and an impressive initial jobless claims continue to show an economy that is quite healthy, omits the continued worries obviously over the Omicron variants," said Ryan Detrick, chief market strategist at LPL Financial in Charlotte, North Carolina.
Detrick cautioned that low holiday season trading volume could exaggerate price moves.
Stock markets have been in a seasonally strong "Santa Claus Rally" that typically occurs in the last five trading days of the year and the first two of the new year.
Among individual stocks, Biogen Inc slipped 7.09%, giving back gains from the prior session as Samsung BioLogics denied a media report that said the South Korean firm was in talks to buy the U.S. drugmaker.
Walt Disney Co stock saw over 20% losses year-to-date while the overall Dow Jones stock index is on track for a 19% gain for the year.
In 2022, investors will shift their attention to expected U.S. interest rate hikes and midterm elections for U.S. Congress, where President Joe Biden's Democrats now hold a slim majority.
"Midterm years tend to be the most volatile out of the four-year cycle. There's actually a 17% average peak to trunk correction during a midterm year, which is the largest of the four years." Detrick added, "Investors were pretty spoiled this year. So be aware that next year won't be as easy."
Volume on U.S. exchanges was 8.08 billion shares, compared with the 10.83 billion average for the full session over the last 20 trading days.
Advancing issues outnumbered declining ones on the NYSE by a 1.26-to-1 ratio; on Nasdaq, a 1.47-to-1 ratio favored advancers.
The S&P 500 posted 64 new 52-week highs and no new lows; the Nasdaq Composite recorded 70 new highs and 141 new lows.
(Reporting by Echo Wang in Taos, New Mexico; Additionaly reporting by Medha Singh and Bansari Mayur Kamdar in Bengaluru; editing by Uttaresh.V, Diane Craft and David Gregorio)
By Echo Wang