Rose injured the ankle October 20 at Milwaukee and missed four games, then returned, before missing Cleveland's past four games.
The former league MVP underwent further tests on Friday and will keep his ankle immobilized in a boot for the next week, the team announced.
In his first season with Cleveland, the 29-year-old Rose, whose promising career has been slowed by injuries in recent years, is averaging 14.3 points in seven games.
Veteran Jose Calderon came off the bench and played for the first time since November 1, and coach Tyronn Lue used LeBron James and Dwyane Wade at the point.
Cavaliers starting point guard Derrick Rose will miss at least the next two weeks with a sprained left ankle. Wade finished with 23 points in 37 minutes.
Cavaliers guard Iman Shumpert will be out for 5-7 days due to knee soreness.
"We still miss a true point guard", Lue said.
Shumpert dealt with a knee injury at the beginning of the season and played just 54 games in 2015-16 and 62 games in 2014-15, but he was durable in 2016-17 and appeared in 76 contests.