But the beating at Anfield on Wednesday night did not shake the optimism of club boss Massimo Moratti, who has history on his side.
The president, who this week celebrated his 13th year at the Inter helm, still believes his side can proceed to the quarter-finals. He even dreams of clinching a trophy last won in 1965, under the tenure of his father Angelo.
Moratti, who was 20 in that year, recalled how the blue-blacks eliminated Liverpool to qualify for the final which they 1-0 over Benfica.
The club, then known as Grande Inter, had already won the 1964 continental title and prevailed over the Reds through a 3-0 home win that reversed a 3-1 beating at Anfield.
After 43 years, it will again take three goals to get the best of Liverpool, who Tuesday scored their two goals in the last five minutes of a game that Inter played for the most part without the dismissed defender Marco Materazzi.
"Still, we played like heroes (at Anfield). Now we look at history, as in 1965," the president said. "(Their fans) are amazing when they cheer on. At San Siro we'll have to live up to their enthusiasm. This team can do a great thing like the Grande Inter did."
Playing one man down lately has become a habit for Inter, who had players dismissed in four of their last seven games. The red cards, though, were hardly a problem in the Serie A, which they firmly command, and in the Italian Cup, where they are in the semi-finals.
"I did not see mistakes and I have no criticism for the team and (coach Roberto) Mancini," Moratti said. "Maybe I could criticise the referee. The problem is that we cannot always play with 10 men."
What Inter learned in England, is that the European stage is much tougher than the home league that they have dominated since 2006.
After 29 unbeaten games, which include just five draws, the road has suddenly become uphill for Mancini as he tries for a fourth consecutive year to win the big continental title.
Most Italian commentators agreed that Materazzi's two yellow cards were a bit too harsh, but there was agreement also on Inter's poor showing in the first half hour before his dismissal.
Liverpool are in for a defensive match in Milan on March 11, when Mancini may consider adding David Suazo to his usual strikers Julio Cruz and Zlatan Ibrahimovic, who played below par at Anfield.
Inter, however, will have to fear Liverpool's counter attacks as Materazzi will be sidelined and Ramiro Cordoba, also a central defender, may not recover from a serious knee injury suffered in England.
By Alberto Cagliano, dpa