The Penguins made the announcement on Wednesday after tests on Monday identified Dupuis' second clot in less than a year.
Dupuis, who was also diagnosed with a blood clot in January, complained of discomfort in his chest having missed practice at the start of the week.
The 35-year-old Canadian will undergo treatment with blood thinners.
"Pascal had a blood clot in his leg that travelled to his lung," said Penguins team physician Dr. Dharmesh Vyas in a statement.
"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."
This season, Dupuis scored six goals and dished out five assists in 16 games for the Penguins, who are 13-3-1 so far.
"It's not a great situation to be in, but that's the card I've been dealt," Dupuis said.
"Hockey's definitely second in my mind right now and [his family is] the most important part of my life right now. So, I just have to be healthy for them."