Rafa Benítez, well known for his squad rotation when manager of Liverpool, chose to sacrifice top spot in Group A in favour of the World Club Championship as Internazionale slumped to defeat at Werder Bremen.
Already qualified for the round of 16, Inter, who finish second to Tottenham Hotspur, fielded a largely makeshift team with their coach resting several top players for the Club World Cup in Abu Dhabi later this month.
Sebastian Prödl headed Bremen, already eliminated after a disappointing European season, into the lead in the 38th minute and Austrian Marko Arnautovic, who played on loan for Inter last season, doubled the score four minutes after the restart.
The substitute Claudio Pizarro sealed the win with a shot two minutes from time after Werder twice rattled the woodwork in a one-sided game.
Bremen, who have never lost at home to an Italian team in 15 games, finish bottom of the group and will not continue in a European competition after the winter break for the first time since 2004.
With the title holders missing the Argentinian striker Diego Milito through injury and the defender Lúcio with influenza, Benítez also opted to rest the Dutchman Wesley Sneijder and give his goalkeeper Paolo Orlandoni his first start in the competition.
Inter looked sluggish and had to wait nearly 20 minutes for their first shot, a Thiago Motta effort that sailed well over the bar.
Bremen, unable this season to hit top form in the league and in Europe, picked up the pace after half an hour and came close with Portuguese Hugo Almeida chesting down a cross and firing his volley narrowly over the bar.
With the coach Thomas Schaaf's shouts more audible than the crowd, who were shivering in the stands, the hosts took the lead in the 38th minute when the Austrian Prödl rose to head in a Torsten Frings corner, with the ball taking a slight deflection.
Four minutes after the restart it was Arnautovic who caught the Inter defence napping when he beat marker Estaban Cambiasso to volley in an Almeida cross.
Inter managed to threaten only once, with Goran Pandev accidentally hitting the post with a curled cross while Werder kept pressing, hitting the woodwork late in the game through efforts from Per Mertesacker and Aaron Hunt before the former Chelsea striker Pizarro notched up their third goal.