Michel Der Zakarian's men have already knocked their opponents out of one cup competition this campaign, running out 4-1 winners in December's Coupe de le Ligue tie.
Nevertheless, they are still 21/20 (2.10) with bet365 to take their place in the quarter-finals by coming out on top once again here.
Just one of the previous nine encounters between the teams has resulted in a draw, but you can get odds of 9/4 (3.25) on a deadlocked 90 minutes.
The hosts will be without defenders Jerome Roussillon and Ambroise Oyongo, who are both sidelined through injury.
Bruno Genesio will welcome back Lucas Tousart from the suspension that kept him out of Sunday's trip to Monaco, giving him a full squad to choose from.
That 4-1 cup win in the last encounter certainly came as a surprise for Montpellier, who have conceded fewer goals than every Ligue 1 side except PSG but only scored more than three other teams.
However, their recent matches have been far more high-scoring than usual, with their most recent five outings producing 19 goals in total.
This trend is likely to continue against a visiting side that has scored 38 times in their previous 15 away games, whilst conceded 10 in their most recent five.
Tips and Predictions
With over 2.5 goals being scored in seven of the last nine meetings between this pair, even odds (2.00) seem generous on three or more going in for Montpellier's fifth game in six and Lyon's 14th in 16 on the road.
Odds correct at the time of writing. Please gamble responsibly.