The Russian club lost both of their opening Group C matches - to Malaga and AC Milan - and desperately need to find some form if they are to progress in the competition having conceded six times already.
Anderlecht have yet to fire on all cylinders either, with just one point to their name, and are as much in need of results as Wednesday night's opponents.
The Belgian side showed promise on matchday one with a goalless draw at Milan, but then fell apart in a 3-0 loss at home to Malaga.
With Zenit and Anderlecht set to face each other twice in the next fortnight, Spalletti knows the double-header could make or break either side's campaign.
"I heard that Anderlecht's general manager said they need to get four or six points from their games against Zenit," the Italian said on www.fc-zenit.ru.
"We think the same way as they do. Looking at the situation which we're in, it would be very good for us to earn four or, better yet, six points in these two matches.
"This game is different from the first two group matches in that the teams are in different situations.
"Anderlecht's management says that reaching the Europa League suits the team, while Zenit is certainly counting only on making the Champions League play-off stage.
"We have practically no room for error."
As well as facing a daunting trip to Russia, Anderlecht must also do without injured strike duo Dieumerci Mbokani (broken nose) and Massimo Bruno (bruised toe).
Even in their absence, general manager Herman Van Holsbeeck is hoping his team can add to Zenit's troubles.
"We will now play Zenit twice and if we live up to our ambitions we should get at least two points from them," he said on www.rsca.be.
"It could even be four or six points, but it won't be easy because Zenit have invested heavily in their team.
"Zenit are under pressure but we still have to play our game. Our mentality on the pitch will be very important. We must battle against each other until we drop.
"We are without Mbokani and Bruno but that is no excuse. The only way to get results is to play as a team.
"We have to fight for every square metre from the start, just like we did against Milan."