Liverpool lost 3-2 at third tier Oldham, whilst Tottenham were beaten 2-1 by second tier Leeds. Chelsea also struggled against third tier opposition in Brentford, drawing 2-2.
On Saturday Luton became the first fifth tier side to win a game against a top division side for over 20 years as they beat Norwich 1-0.
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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.