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Ciprofloxacin, griseofulvin, and rifampicin are three human antibiotics that are also widely used in the shrimp culture of Cangio coastal wetland (Vietnam, 10° 24’ 38” N, 106° 57’ 17” E). They have been detected in shrimp larvae pond and receiving water bodies. However, the environmental fate of these antibiotics in coastal wetland milieu is currently unknown. The aim of this study was to determine the degradation potential of these antibiotics in water and sediments from Cangio coastal wetlands. The effects of light, microbial activities, and presence of sediments on the degradation of all three antibiotics were investigated in “water-only” and “water–sediment” experiments. Results indicate that the environmental fate of those antibiotics was quite complex. Photodegradation seemed to play a major role in “water-only” system, since shorter t ₁/₂ was observed for ciprofloxacin, griseofulvin, and rifampicin, with light than in the dark, for both sterile and non-sterile conditions. Biodegradation played a minor role in the disappearance of the antibiotics and was overlaid by photodegradation. In addition, sorption to sediment was of major importance for antibiotics, especially for ciprofloxacin and rifampicin. The t ₁/₂ of these antibiotics in aqueous phase of “water–sediment” system was higher than for “water-only” experiments, indicating that a part of antibiotics were adsorbed by sediment. The biodegradation did not play a major role on sediment sorption of CIP and RIF, since no statistically significant differences between non-sterile and sterile conditions were observed. Only for GRI, the impact of the biodegradation to the sediment sorption could be found and led to the weak affinity to sediment sorption of this antibiotic. All three antibiotics were more sensitive to photodegradation than to biodegradation; however, the degradation rate was low. In addition, the sorption by sediment occurred also with a slow rate, so these antibiotics could recalcitrant persist in the coastal wetland environment.