Azithromycin (AZT) is a broad-spectrum antibiotic from the group of macrolides that acts against several Gram-positive and Gram-negative bacteria, which has promoted its use in the treatment of different respiratory and sexually transmitted diseases. However, its presence in environmental matrices and in the effluents of conventional wastewater treatment plants has been evidenced in recent years, which reflects the need to develop new treatment alternatives that allow its total removal and minimize the eventual adverse effects, selection of resistant bacterial strains, associated with its presence in water bodies. Simulated sunlight radiation and H2O2 were used to remove AZT from water assessing the effects of operational parameters like the solution initial pH and the peroxide concentration. Results indicate that hydroxyl free radical is the main responsible for pollutant removal but acidic solution conditions and larger H2O2 doses negatively affect OH• generation under the evaluated experimental conditions. Pollutant removal was almost complete after 120 min of photo-treatment. In addition, reduction of the organic carbon content in the treated samples was ∼50.0%; and a significant increase of nitrates concentration in solution was evidenced.