The 26-year-old suffered a stroke 10 weeks ago but was cleared by team doctors, and it was his decision whether to play again this season, according to GM Ray Shero.
Letang, who has 10 goals and eight assists in 34 games this season, signed an eight-year, $58 million deal in July with the Penguins, who have already clinched the Metropolitan Division.
Letang was a Norris Trophy finalist last season. The award is given to the league's top defenseman.
#Pens Letang: My family is scared. But they understand the situation. Doctors talked to them to assure them.
— Pittsburgh Penguins (@penguins) April 9, 2014
#Pens Letang on if he's scared: I'm nervous because I haven't played in a while, but about my situation, not at all. — Pittsburgh Penguins (@penguins) April 9, 2014