Lee tweaked his left ankle late in Boston's 104-94 loss to the Dallas Mavericks on Friday. It's unclear when Garnett suffered his injury.
Randolph is the team's leading rebounder at 11.6 boards. In the past, he has sat out the start of games for being late to practice or a shootaround.
Saturday will mark just the fourth missed game of the season for Garnett, who had returned Wednesday from a left adductor strain and a bout with the flu that kept him out of consecutive contests.
Lee, meanwhile, will miss his first game of the season.
Information from The Associated Press was used in this report.