He said: "We must be ready...ahead of the England match. Focus must be our next job and our next job is England at Twickenham in two weeks.
"I'm not going to sit beside Sergio (Parisse) and talk about a long-term project because I know this group have some great days in them but we have to learn, get mentally stronger and we have a lot to change in Italian rugby to get that.
"I've no doubt one of the many things we need to change is the respect other teams have for us because mentally teams come here with the expectation of winning and play with a different freedom.
"No doubt the mind plays a huge part in games, we have to change our mindset and the respect other teams have for us."
The Italians conceded nine tries at the Stadio Olimpico, including hat-tricks for CJ Stander and replacement Craig Gilroy. The heavy defeat was a reality check for the new coach after the historic first victory over South Africa in Florence in November.
Despite the loss O'Shea tackled questions about the Ireland defeat head-on and led an impassioned defence of his players.
He added: "We are proud people sitting up here and we don't like this. I hate days like this but we know what we have to do and we are working together for Italian rugby.
"This was hard, it's a different challenge. That Ireland team is better than the Welsh team we played, 100 percent. We talked about Ireland's ability to hold onto the ball through a lot of phases which is different to Wales.
"We have a really good group of players. People will smile wryly and hang their heads but we will never hang our heads and our intention is to fight tooth and nail to make the changes and also get some short-terms results."
Meanwhile Italy have confirmed their squad for the trip to Twickenham with an unchanged squad of 30 set to prepare for the clash.
Tom Tierney's unbeaten Ireland Women side face an acid test of their title credentials on Sunday when defending Women's Six Nations champions France arrive at Donnybrook Stadium desperate to ensure they remain in the title hunt.