In this study, bacteriological pollution of Ceyhan River flowing into Iskenderun Bay (Northeast Mediterranean) and antibiotic resistance of Gram (+) and Gram (-) bacteria were investigated. Water samples were collected from May 2014 to April 2015 in monthly periods and 222 Gram (-) and 74 Gram (+) bacteria were isolated from collected water samples. The isolates were contained 8 different species (Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis) which have been identified with Vitek II automated culture system. Microorganism susceptibility tests were performed in accordance with CLSI (Clinical and Laboratory Standards Institute, 2015) criteria. Resistance of the isolates to 15 different antibiotics (Amikacin, Meropenem, Levofloxacin, Imipenem, Piperacillin, Gentamycin, Cefepime, Ceftazidime Penicillin, Oxacillin, Clindamycin, Erythromycin, Ciprofloxacin, Vancomycin, Rifampin) was investigated. The highest antibiotic resistance was found in E. faecalis with 37% against Penicillin antibiotics. No resistance to vancomycin antibiotics has been observed. It was concluded that the Ceyhan River was exposed to fecal bacterial contamination, and it was revealed that this situation would adversely affect both the ecosystem and human health. Measures to protect and improve the ecological and microbiological qualities of rivers and lakes are key to preserving the quality and quantity of water resources for the future.