The reigning Champions had been hoping Williams would return for the Thomond Park clash.
But the Welsh record try-scorer has failed in his race to recover from the knee injury he picked up against Ireland in the RBS 6 Nations and misses out.
"We all know what Shane brings but the reality is that it was always going to go down to the wire," said Ospreys director of coaching Scott Johnson.
"The wonderful gifted player that he is, we have to accept he's out. It's a loss but we have competent people there who can do a job."
But the Welsh region will be able to call upon former All Black Jerry Collins. The fearsome back-rower was hit with a one-week suspension after picking up his third yellow card of the season in last month's regular season defeat to Munster.
He missed the clash with Aironi but will return to face Munster again in his swansong before leaving south Wales at the end of the season.
"Jerry will certainly be in our 23," added Johnson. "He adds something and brings a bit of steel."
It will be the fifth time the two sides clash this season and Munster have already completed a league double over the Liberty Stadium-outfit.
The Ospreys have gone through a difficult period in which they have only won one game in their last five Magners League matches.
But after reaching the all-important play-offs, Johnson is confident the Ospreys can triumph just when it matters.
"Our form hasn't been great but we're in the play-offs. Throughout a season every team ebbs and flows.
"We'll just look at the games we've played with them and try and find the balance, where we can beat them, our skill-set against their's
"They were very confident we were out two weeks ago, but the irony is we play them again and we've shown there's nothing much between us. It will be a good arm-wrestle.
"Form is temporary and class is permanent. If we perform I'm quite confident we can go there and win."