Shanghai and Tokyo fell while Hong Kong and Seoul advanced.
Wall Street's benchmark S&P 500 index ended down 1.2% on Wednesday after being up 1.9% earlier in the day. That was despite surveys showing U.S. hiring and factory activity in November were better than expected.
Markets were sliding when the White House announced the discovery of the first omicron case in the United States. It is unclear whether omicron is more dangerous, but governments have responded by tightening travel controls, fueling unease about the outlook for a global economic recovery.
The latest data “painted an optimistic picture for economic conditions, but that seems to be taking a backseat as the Omicron variant can potentially shift the landscape,” said Yeap Jun Rong of IG in a report.
The Shanghai Composite Index lost 0.3% to 3,567.70 and the Nikkei 225 in Tokyo sank 0.7% to 27,760.67. The Hang Seng in Hong Kong gained less than 0.1% to 23,680.79.
The Kospi in Seoul surged 1% to 2,930.31 while Sydney's S&P-ASX 200 lost 0.1% to 7,227.90. New Zealand and Southeast Asian markets retreated.
The S&P 500 fell to 4,513.04. The Dow Jones Industrial Average declined 1.3% to 34,022.04. The Nasdaq slid 1.8% to 15,254.05.
The S&P 500 on Friday turned in its biggest loss since February, sliding 2.3%. It rose 1.3% on Monday and gave up 1.9% on Tuesday.
On Wednesday, the Institute for Supply Management reported U.S. manufacturing growth activity accelerated faster than expected in November. Payroll processor ADP said employers hired more people than expected. That might raise expectations for Friday's U.S. government jobs data.
Investors already were rattled after Federal Reserve chairman Jerome Powell said Tuesday the U.S. central bank might withdraw stimulus sooner than expected due to persistently high inflation.
The Fed's bond purchases are injecting money into the financial system, boosting stock prices. The S&P 500 has more than doubled since March 2020.
In energy markets, benchmark U.S. crude rose 64 cents to $66.21 in electronic trading on the New York Mercantile Exchange. The contract fell 61 cents on Wednesday to $65.57. Brent crude, the price standard for international oils, gained 68 cents to $69.55 per barrel in London. It lost 36 cents the previous session to $68.87.
The dollar gained to 113.02 yen from Wednesday's 112.79 yen. The euro advanced to $1.1332 from $1.1319.