The 225-issue Nikkei Stock Average dropped 93.80 points, or 0.36 percent, from Wednesday at 25,634.34.
The broader Topix index of all First Section issues on the Tokyo Stock Exchange, meanwhile, gained 5.76 points, or 0.33 percent, to finish at 1,726.41.
Throughout the day, the U.S. dollar remained steady in the upper 103 yen zone, as concerns over the coronavirus resurgence kept market players cautious.
The Japanese capital of Tokyo, the epicenter of the country's outbreak, reported 534 new COVID-19 cases on Thursday, renewing a record number of daily infections and exceeding the 500 mark for the first time, as the local government raised its virus alert by one notch to the highest level, meaning "infections are spreading."
"Investors grew cautious as the government may take countermeasures including restrictions on business activities," Shingo Ide, chief equity strategist at NLI Research Institute was quoted by local media.
However, share losses proved moderate, with the Nikkei regaining some of its earlier losses and the Topix closing higher toward the close.
"The market was supported by vaccine hopes and views that the economic recovery is still on track," said Ide. On Wednesday, pharmaceutical giant Pfizer Inc. said that it will seek to apply for emergency use authorization in the United States for a potential COVID-19 vaccine "within days."
By the close of play, land transportation and wholesale issues comprised those that gained the most, while steel makers and nonferrous metal issues led decliners.
Meanwhile, retail issues were mostly down on worries of possible requests for shorter business hours from the government, with department store operators J. Front Retailing falling 11 yen, or 1.3 percent, to 856 yen and Takashimaya decreasing 19 yen, or 2.1 percent, at 869 yen.
Game maker Nintedo gained 1,180 yen, or 2.2 percent, to 54,420 yen on expectations that people will spend more time at home amid the spike of COVID-19 infections.
On the First Section on Thursday, declining issues outnumbered advancers 1,238 to 827, while 111 ended unchanged.
Trading volume on the main section increased to 1,368.24 million shares from Wednesday's 1,187.06 million shares.
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