World No 1 Djokovic survived four match points before seeing off Frenchman Tsonga on Tuesday but there seems to be little prospect of second seed Nadal having to face a similar scenario against his fellow Spaniard.
Nadal, who has not dropped a set so far in the tournament, has a 7-0 record against Almagro, a player he will face for the sixth time on clay on Court Philippe Chatrier as he bids to become the first player to win seven titles on the Paris clay.
Opening proceedings on Centre Court will be second seed Maria Sharapova and Estonian Kaia Kanepi. The Russian can take over as world No 1 by reaching the final here.
Wimbledon champion Petra Kvitova continues her quest for a second grand slam crown when she faces Kazakh Yaroslava Shvedova, the qualifier who ousted title holder Li Na in the previous round.
Briton Andy Murray, the fourth seed, will hope his lower back pain subsides before he meets Spain's David Ferrer on Court Suzanne Lenglen.