Paul suffered a fractured bone in his right hand while Griffin aggravated his left quad injury Monday night against the Blazers in Game 4.
This a worst-case scenario for the Clippers, who were expected to make a deep playoff run. Los Angeles took a 2-0 series lead before the Blazers won the past two games in Portland to even it up.
Paul underwent surgery on his right hand Tuesday and will be examined in four to six weeks.
"We still have home court. No one has won a road game yet in this series," coach Doc Rivers told reporters Tuesday. "Now we have to find a way of winning tomorrow and that’s as far as we can think right now. My job with the guys is to make sure that they’re ready and focused. It’s easy when you have the injuries we have to think all kinds of other stuff."
The Clippers still hold the home-court edge with the series returning to Staples Center tied 2-2 and Game 5 scheduled for Wednesday. Rivers is still debating what his starting lineup will look like for the pivotal game.
"We’ve had 10 different lineups on the board," he said. "Most likely it will be a pretty big lineup."
Paul, who was averaging 26.3 points and 8.3 assists through the first three games of the series, appeared to suffer the injury while defending Gerald Henderson’s drive in the third quarter.
Griffin missed 41 games this season after partially tearing a tendon in his left quad. He said he felt a tweak Monday night in the same area after getting fouled by Mason Plumlee on Monday night.
Griffin, who averaged 15 points, 8.8 rebounds and four assists in the series, underwent an MRI on Tuesday and the exam revealed no further structural damage. The team announced that Griffin will be ready for the start of training camp next season.
"You feel bad for Chris, you feel bad for Blake," guard J.J. Redick said.
The NBA playoffs have lost some major star power with Griffin and Paul out and the reigning MVP — Stephen Curry — expected to miss two weeks after he sustained a Grade 1 MCL sprain in his right knee Sunday.