With both sides sitting on 82 points, six ahead of nearest rivals West Ham, either side is likely to take one step closer to a Premier League return with victory at St Mary's.
But the Royals boss is not thinking that far ahead and insists his players, fresh from Tuesday's vital 1-0 win at Brighton, will be focused on getting the three points in the bag.
"First and foremost, it's a game", said McDermott, who praised his side's determination in sealing the win at the Amex Stadium.
"It's the next game and it's the same three points. To me, it's just the 43rd game and we're concentrating on what we can affect and play the way we do.
"We're going to go there, concentrate, go from there and move onto the next game. We'll just do what we have done over the last three-and-a-half years.
"We have had opportunities recently and we have taken them but Friday evening's game is difficult.
"I can't tell you how it's going to go but we will prepare for the game like we always do."
Reading travel to long-time leaders Southampton in superb form, winning 13 of their last 15 league games, dropping just five points, with McDermott having to use all of his squad through the Easter fixtures.
Ian Harte, Tuesday evening's match-winner, revealed he was playing through the pain barrier while Mikele Leigertwood, Jay Tabb and Hal Robson-Kanu, plus long-term absentee Jem Karacan, all missed the trip to Brighton.
McDermott, who was full of praise for Southampton ahead of the game, is hopeful that both Leigertwood and Robson-Kanu can still make Friday night's game, which will be shown live on Sky Sports 1 (7.45pm ko).
"We have always worked that way. We've got a big and good squad and we have got good players.
"There's no fresh injury worries that we're looking at. We're working with Mikele Leigertwood. We trained today and then we'll train again tomorrow before we head down.
"Southampton play a certain way and have a fantastic manager in Nigel Adkins. It's certainly going to be a good game.
"They have got a good team. They're like us and they have a striker who scores lots of goals. We'll play that but we will do what we can do."
Last time the sides met at the Madejski back in October, the Royals were unlucky not to come away with all three points and had to settle for a 1-1 draw.
In a frantic final quarter of an hour, the Royals took the lead through Mikele Leigertwood.
The visitors then went down to 10 men just moments after conceding when Saints skipper Dean Hammond received a second yellow card.
The odds were against them but substitute Steve de Ridder smashed home an equaliser with 10 minutes remaining.