The clot was discovered Monday after the 35-year-old veteran complained of "discomfort in his chest," according to a news release issued by the team.
"Pascal had a blood clot in his leg that traveled to his lung," Penguins team physician Dr. Dharmesh Vyas said in the release. "In medical terms, that is a deep vein thrombosis resulting in a pulmonary embolism. This is the second such incident that we know of for Pascal. The treatment is at least six months of blood thinners, during which time he will not be able to play hockey. Other than that, his condition is stable."
Dupuis, 35, was also treated for a blood clot in January and was put on blood thinners following surgery to repair an ACL injury, which caused him to miss most of last season.
"Yeah, it's been hard," Dupuis said Wednesday. "But the hockey stuff -- the knee, the puck in the neck -- this is all stuff you come back from. You're a hockey player ... it's the risk you take when you're on the ice.
"The other stuff -- the clot, the lungs -- it has nothing to do with hockey. It's life-threatening."
Dupuis, who had not played since Saturday, has six goals and five assists in 16 games.
"This is very new news, this is tough news," coach Mike Johnston said Wednesday. "He's an inspirational leader, a great voice in the room."
The Penguins have had their fair share of medical scares in the past year. Former Penguins goaltender Tomas Vokoun suffered from a blood clot in his pelvis -- a life-threatening situation that required surgery and ultimately sidelined him for the entirety of last season.
Defenseman Kris Letang missed time last season after suffering a stroke, and fellow defenseman Olli Maatta recently missed two weeks after having a cancerous tumor surgically removed from his thyroid earlier this month.