Dons must put the glitz and glamour of the Liverpool game behind them and get a result away at Sunderland tomorrow (Saturday).
After back-to-back 1-0 defeats in League One, Dons sit 15th in the table. Sunderland meanwhile have had a mixed start to the season so far, but have lost just once in their opening nine games and are fifth, four points ahead.
While Dons' midweek money-spinning clash against European champions Liverpool took attention away from the league campaign for a few days, Tisdale says his side have to come back from the Stadium of Light with something next to their name.
He said: "We need a win, or at least a result of some kind because we've lost the last two. It's serious stuff now."
"There can be no excuses whatsoever that the Liverpool game got in the way against Southend, or for this game. I've got a squad of players I can rotate if I choose – maybe not in some areas – but I trust the players if I do. We just wanted to enjoy it. I'm not glad it's over, but on the other hand I'm not sad it's over.
"We're pretty aware that we lost the last two league games and we need to get back on track."
Tisdale made four changes to the side on Wednesday night, leaving out the likes of keeper Lee Nicholls and defenders Russell Martin and Dean Lewington - all three have been regulars in the league this season. But he believes the squad will have a familiar feel at Sunderland.
He said: "The bulk of the team will be the same, but we are not flush with great depth at the front of the pitch, but we played on a great stage here on Wednesday night and we're going to Sunderland, another great stage, so there shouldn't be too much to worry about. We might be a little bit tired, so we've tempered training, but we'll be fine."
Sunderland were tipped to win promotion back to the Championship at the first time of asking last season but failed at the final hurdle, losing in the play-off final to Charlton at Wembley Stadium.
But after a solid start to the season, Tisdale said: "The wheels are turning. We should be very conscious of that, but also we need to understand what we can do, and in what way we can do it and play to our strengths."
They head into the game at the Stadium of Light off the back of two draws against Rotherham and Bolton Wanderers, who picked up just their second point of the campaign on Saturday.
Dons and Sunderland have crossed paths just twice down the years, both of which have come in the League Cup, and both have seen the Black Cats come away victorious. After their 2-0 win over Dons in 2012, Sunderland scored four goals in the last 12 minutes to overturn a two-goal deficit in the same fixture a year later to win 4-2.