Most of the Italian press predicted that Prodi would lose in the senate, where his ruling coalition suffered a defection earlier this week, eroding its support.
Two leftist senators have already announced they would vote against Prodi if the vote goes forward.
With two more votes added to the "no" column, the opposition has a theoretical edge of up to five votes even if six senators-for-life cast ballots in support of Prodi, according to a tally by the AFP news agency.
The crisis for the Prodi government gained momentum after the resignation of Clemente Mastella, the justice minister, last week.
Mastella resigned after being named in a corruption probe along with his wife. Both have protested their innocence.
On Monday Mastella's Catholic UDEUR party, whose three votes have been crucial in the senate, said it would oppose Prodi in a vote of confidence, complaining of lack of support from the ruling coalition.