Coach Mike Sullivan announced Letang's status following the morning skate.
Letang is the latest Penguins player to be sidelined in the early stages of the season, a group headlined by stars Sidney Crosby (wrist) and Evgeni Malkin (knee), both recovering from offseason surgeries.
The Penguins are off to a solid start without Crosby and Malkin, posting a 2-0-2 mark heading into Saturday night's visit from Toronto.
Crosby and Malkin are hardly the only Penguins players banged up. Forward Bryan Rust is "week to week" with a lower-body injury. Veteran center Jeff Carter, who has filled in for Crosby as the first-line center, will also miss Saturday night's visit by the Maple Leafs after testing positive for COVID-19.
Sullivan said Friday that Carter is asymptomatic but will be unavailable against Toronto. The team did receive a bit of good news Friday when it turned out that top goaltender Tristan Jarry had a "false positive" COVID test on Thursday, freeing up his return to practice.