The Saints, bidding to follow in Norwich's footsteps and win back-to-back promotions, currently occupy the second automatic promotion spot in the npower Championship and Adkins will rest some key players for the fourth-round replay at St Mary's Stadium.
Teenagers Luke Shaw, James Ward-Prowse and Jack Stephens are set to be involved again.
Adkins said: "Having put ourselves in the race to get promoted, the league is the priority. But it's great to have a cup run and we want to win all the games we compete for and we want competition for places.
"We've got a good, strong squad of players and now and again we want to utilise the youth. We've done that in the two cup competitions this season."
Millwall turn their attention to the cup after Saturday's defeat at derby rivals West Ham left them hovering just above the relegation zone.
The Lions are set to be without captain Paul Robinson (thigh) and deadline-day signing from Wolves, Andy Keogh, is ineligible, so Tottenham loanee Harry Kane or former Saint Dany N'Guessan will start up front.
Hamer Bouazza, Jordan Stewart (both groin), Tamika Mkandawire (knee) and Therry Racon (ankle) are still out.
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