Blackburn conceded only three goals in their first nine competitive matches of 2007-08 and Hughes said of the duo: "They have been the strength of our side, in the initial part of this season.
"They have given us a real defensive base from which we can play our football. It would be a big blow if we lost the pair of them."
Samba returned to full training on Friday after being concussed by a stray boot from Chelsea's Andriy Shevchenko in the goalless draw at Stamford Bridge last weekend.
Perhaps crucially Samba missed the shock 2-0 UEFA Cup defeat to Greek side Larissa on Thursday, during which Kiwi Nelsen, 29, aggravated his long-standing hamstring damage.
"He is a little bit sore but it is similar to the episode concerning his hamstring last year," Hughes reflected.
"He missed 10 or 15 days or so and felt a similar pain this time.
"It is not a hamstring as such, it is not a muscle injury, it is just a pain he gets when the scar tissue releases. If that's the case the prognosis is probably better than we initially thought."