Spurs lost 1-0 to Manchester City three days after Sissoko picked up a groin injury in the second leg of their stunning Champions League quarter-final victory over Pep Guardiola's men and Pochettino said that he was not optimistic about the Frenchman's chances of a quick recovery.
Home games against Brighton and Hove Albion, and West Ham in the Premier League will give Spurs the chance to continue their push for third place ahead of the visit of Ajax, but Pochettino said he is not expecting Sissoko or fellow midfielder Harry Winks to feature.
Winks has been struggling with a similar problem to Sissoko but managed 81 minutes on Wednesday before sitting out Saturday's defeat at the Etihad Stadium.
"Moussa Sissoko is not going to be fit, maybe for the next two weeks," said Pochettino.
"We hope he can recover before but I am not so optimistic.
"Harry Winks we don't know because it is a problem that is one day very good, next day not very good, it is about assessing each day.
"We hope he will be available for Tuesday [against Brighton] but we are not sure."
Defeat at City on Saturday left Spurs just one point clear of fourth-placed Arsenal – who were then stunned 3-2 by Crystal Palace on Sunday – and Pochettino said the prospect of the Champions League semi-final would not distract his players from ending their domestic campaign on a high.
He said the opportunity to play three successive matches at the new Tottenham Hotspur Stadium would give Spurs a lift, saying: "We hope we can keep going, getting the same result. It is going to be fantastic and it is going to be helpful for us playing in the new stadium with our fans and we hope and wish to repeat the performances of the previous results.
"We are not thinking of Ajax. We showed today that we are thinking about the Premier League.
"Now our energy is on Brighton. It is so clear that we have two objectives – one is to be in the top four at the end of the season and the other is to beat Ajax, but we need to go step-by-step."