Prop Adam Jones (back), lock Brent Cockbain (shoulder), No.8 Ryan Jones (dead leg) and wing Shane Williams (knee) are all unlikely to play the Oaks.
The loss of foursome dents Welsh plans to - as Ruddock put it - 'bed in some combinations' ahead of New Zealand's visit Cardiff in a fortnight's time.
With the All Blacks regarded as the main course in the November banquet, many commentators believe that Wales will opt to field a shadow XV for Romania.
But Ruddock indicated that he would seek to maintain the momentum his side picked up towards the end of their meeting with the Springboks.
'In selection we will not underestimate Romania at all, we need a win now,' Ruddock told BBC Sport. 'They had a win over Italy in the summer, they have a French coach and a lot of players with links in France.'
New Wales skipper Gareth Thomas was also reluctant to look too far down the track.
'We now have Romania, New Zealand and Japan. People are already talking about the New Zealand game, but the next game is Romania,' said Thomas. 'We will look at them this week and then have a big game against New Zealand.
'We know that's a huge game, but we have to start against Romania as we finished against South Africa.'