Simon, ranked 42 in the world, has beaten Djokovic only once in their six previous meetings although France is hoping the hard indoor surface at the Belgrade Arena will suit his style of play.
Frenchman Gael Monfils meanwhile could help balance Friday's opening day of play when he opens the tie against Janko Tipsarevic.
Monfils, the world number 12, flopped at the Davis Cup last year during a playoff against the Netherlands but has been far more solid this year and recently beat Tipsarevic at the US Open.
France captain Guy Forget produced no surprises in naming Michael Llodra and Arnaud Clement for Saturday's doubles encounter, when the French pair will meet Nenad Zimonjic and Viktor Troicki.
Llodra remains an option for France in the event he is needed for one of the two singles matches on Sunday.
Both team captains have the choice of making changes to their doubles teams up to one hour before the start of the match. The same rules applies to Sunday's reverse singles but does not apply to Friday's opening singles.
Serbia captain Bogdan Obradovic meanwhile opted for Tipsarevic over Viktor Troicki, who is better ranked and has secured better results this season but has less Davis Cup experience than his compatriot.
Tipsarevic notably rose to the occasion when he beat both Tomas Berdych and Radek Stepankek in Serbia's semi-final defeat of the Czech Republic.