Wales Grand Slam winning Captain Alun Wyn Jones and George North have sidelined with injuries picked up in the Six Nations.
Jones suffered knee ligament damage while North broke two bones in his hand in last weekend's Six Nations victory over Ireland which saw them clinch the trophy.
George North went off in early in the match but the captain continued after receiving treatment as Wales triumphed 25-7 at the Principality Stadium.
He scored two tried during Wales' fightback against France in their opening Six Nations game as they wiped out a 16-0 interval deficit.
Lock Jones led his country to their first Grand Slam since 2012 and a first Six Nations title in six years. He was named the player of the tournament.
The Ospreys confirmed the injuries but haven't ruled them out of their Guinness PRO14 clash against the Cardiff Blues on April 27.
It's the club's final regular-season game, although they still have a chance of securing a title play-off place. They face league games against the Cheetah's and Southern Kings at the start of April.
The club are also without Wales centre, Scott Williams, who took no part in the Six Nations due to injury.