The presence and accumulation of antibiotics in the water environment has become emerging contaminants of concern causing disruption of ecosystems worldwide. We describe here the seasonal variation and the occurrence of antibiotic residues in Fez city surface water (Morocco). During one year between February 2014 and January 2015, 8 surface water samples were collected monthly. Quantification of the 7 antibiotics was performed by on-line Solid Phase Extraction (SPE) liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 96 surface water samples were investigated and the results revealed that 100% of the sites were contaminated by at least one antibiotic. Amoxicillin had the highest concentration with maximum concentration (4107 ng L 1), followed by ciprofloxacin (1058 ng L 1) and sulfamethoxazole was the most widely detected (93%). Seasonal variation showed that the concentration of antibiotics was higher in winter for trimethoprim (96 ng L 1), ciprofloxacin (438 ng L 1) and in summer for amoxicillin (1113 ng L 1), sulfamethoxazole (162 ng L 1) and erythromycin (47 ng L 1). The results from this research show that antibiotics are frequent contaminants in Fez city surface water. This is the first attempt to assess the occurrence of these 7 pharmaceutical residues in water samples in Fez Morocco.