Coach Ruddock has also had to contend with a significant injury list, while suspension currently removes Gavin Henson, Dafydd Jones and Ian Evans from his plans.
Ruddock's England counterpart Andy Robinson has described the RBS 6 Nations opener as his team's most important game since the 2003 World Cup triumph, but the Welsh camp have drawn their own conclusions about what is potentially a season-defining game.
"We are expecting England to be really fired up," said Ruddock.
"I think they have gone on record as saying this is the most important game for them since the World Cup.
"They have also stated that we are favourites, which we find quite bizarre because our record at Twickenham is not great and because of a number of other factors, including injuries, that have happened to us.
"It looks like there is a bit of pressure on England - they don't want to lose at home and they don't want to lose against us.
"They are very fearful of that, and they are trying to put the pressure back on us, but to be honest, we are quite relaxed about it."
Ruddock has seen his squad decimated by injuries to the likes of Grand Slam heroes Ryan Jones, Tom Shanklin, Brent Cockbain and Kevin Morgan, but he remains upbeat as Wales try to end 18 years of failure at English rugby headquarters.
"As coaches and players, we try and do the best we can. We can't predict the future, we can't look into a crystal ball and say we are going to win three games out of four or we are going to win a Grand Slam," added Ruddock.
"All we know is we will try and get the players to relax and play to the best of their ability. We took it game by game last year and it worked for us, and that is what we will do again this year."
Wales centre Ceri Sweeney has also had to withdraw from the squad after pulling up in training on Wednesday with a groin injury.
Cardiff fly-half Nicky Robinson will take Sweeney's place on the bench.
Ruddock said: "We are terribly disappointed for Ceri, who is such a great player and popular member of the squad.
"However, it's comforting to know that we have a replacement of the quality of Nicky.
"We will know more about Ceri's injury on Monday, but the hope is that he will be back in contention next week."