Atletico fielded a weakened team days after their triumph in the Copa Libertadores, and succumbed to goals from Everton Ribeiro, Nilton and Ricardo Goulart, who netted two.
Cruzeiro are now ahead on goal difference from Internacional, who lost 3-0 to Nautico. Botafogo and Flamengo drew 1-1 in the big Rio de Janeiro derby.
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The reputation of the Premier League means it is the most popular and one of the most watched leagues in the world.
Five English clubs will compete in the last sixteen of the Champions League for the first time ever as Liverpool, Manchester United, Manchester City, Chelsea and Tottenham face some difficult away matches.