It is the latest crackdown by Belarus leader Alexander Lukashenko, since he claimed victory in discredited elections over a year ago.
An IT worker and a KGB security agent were shot dead during a raid on a flat in the capital Minsk on Tuesday.
Friends said Andrey Zeltser, 31, was an opposition supporter.
It is unclear how he and the agent were killed, and critics have cast doubt on a state video purporting to show the raid taking place.
Human rights group Viasna96 said mass detentions began on Wednesday in reaction to social media posts about the shooting. They continued on Thursday and the Belarusian leader said on Friday that the number in custody was now in the hundreds.
Zeltser worked for American IT firm Epam Systems and reportedly had US citizenship. Epam’s boss in the US has in the past been accused by the Belarusian leader of financing protests.
A heavily-edited video released by Belarus state media showed the KGB storming his flat as he appeared to wait with his back to the camera, brandishing a gun.
There is no explanation how they got hold of images from inside the apartment and there is no image of Zeltser himself opening fire.
His friend, Alya Ilyukevich, was not aware he had a gun. “You recognised the guy’s voice, but the picture doesn’t add up in your head,” she told BBC Russian.
The KGB man killed in the raid was named as Dmitry Fedosiuk and a funeral ceremony for him took place on Friday in Minsk. Mr Lukashenko said Fedosiuk had run into the flat and been shot in the heart.
PROTEST LEADER: No regrets for jail after Belarus protests
Thousands of opposition supporters were detained in the weeks after opposition candidate Svetlana Tikhanovskaya claimed victory in the Belarusian presidential election in August 2020.
She was thrown out of Belarus the day after the vote and while major opposition protests continued for weeks, Alexander Lukashenko’s state authorities gradually brought them to an end through mass detentions.
One of the country’s oldest human rights groups, the Belarusian Helsinki Committee, was liquidated by a Supreme Court ruling on Friday.
Justice ministry officials claimed they had evidence that the group had paid two people to observe the election last year.