The top seed and defending champion lost to 11th seeded American John Isner in three sets 6-7 (7), 6-3, 6-7 (5) in 2 hours and 45 minutes in the semi-finals of the BNP Paribas Open.
Novak dismissed 12th-seeded Spaniard Nicolas Almagro in straight sets 6-3, 6-4 in 81 minutes at the BNP Paribas Open on Thursday to reach the semi-finals of the ATP World Tour Masters 1000 event.
The world no.1 beat Pablo Andujar in three sets 6-0, 6-7 (5), 6-2 and moved into the last eight at the BNP Paribas Open in Indian Wells.
Nole continued his run at the BNP Paribas Open in Indian Wells on Monday, dismissing Kevin Anderson of South Africa in straight sets, 6-2, 6-3 in 1 hour and 37 minutes.