Nantes are now winless in their last seven games (six defeats and one draw).
Simon was on from the start before making way in the 73rd minute.
The defeat leaves Nantes in third place on three points while Freiburg confirm their place in the next round.
In Group D Victor Boniface bagged a brace as Belgian club Union St.Gilloise were held to a 3-3 draw at home by Sporting Braga.
Boniface scored in the 20th minute to make it 1-1 and netted in the 62nd minute to tie the game at 3-3.
The draw is enough to send Boniface and his St.Gilloise teammates into the knockout phase.
And other outcomes in the early kickoffs saw Arsenal pip Bodo/Glimt 1-0, Rennes beat Dynamo Kyiv 1-0 away, Real Betis and Roma played 1-1 and Midtjylland held Feyenoord to a 2-2 draw.
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