Captain Sergio Parisse has been ruled out of Italy's Guinness Six Nations clash with Ireland in Rome on Sunday.
The 35-year-old number eight suffered a suspected concussion in Stade Francais' 23-14 home Top 14 defeat by Lyon on Saturday.
The Azzurri must now do without their 136-cap record appearance-holder when searching to end a run of four straight Test defeats.
Forwards coach Giampiero De Carli insisted, however, that Italy can cope in the absence of their talismanic skipper.
"The loss of Sergio Parisse? It is clear that we lose one of the strongest number eights in the world, but we have players who are up to the situation that will be able to contribute to the team," said De Carli.
"We know Ireland well, we faced them last time in Chicago in the first Test match in November: it will be crucial for us to make the most of our opportunities."
The Italian Rugby Federation (FIR) confirmed Parisse's injury absence in a statement on Tuesday, revealing however that the long-serving captain will remain with the squad to help O'Shea's men prepare to host Ireland.
"Sergio Parisse, captain and number eight of the national team, will not be available for the third match of the Six Nations in Rome against Ireland," read the FIR statement.
"The Azzurri captain, having undergone the second phase of neurological investigations following concussive trauma reported in the Top 14 match with Stade Francais, will continue to the return-to-play protocols according to current international regulations.
"The Italy captain will also remain with the squad."
