The occurrence of antibiotic residues in the environment is of concern not only because of their contribution to the spread of bacterial resistance, but also due to their possible toxicity to non-target organisms. In this study, the aquatic environmental toxicity of ciprofloxacin (CIP) and sulfamethoxazole (SMX) was assessed in the following model organisms: Daphnia magna and Artemia salina (embryonic and immobilisation test with a 10-d follow-up), Phaeodactylum tricornutum (algal growth inhibition test), and Spirodela polyrhiza (duckweed growth inhibition test). Results showed that among the two saltwater organisms, A. salina was insensitive to both antibiotics, whilst P. tricornutum responded only to SMX with an EC₅₀ of 2.7 mg L⁻¹. In freshwater species, D. magna embryos were more sensitive than juveniles to SMX (EC₅₀ 53.8 and 439.2 mg L⁻¹, respectively), whereas the opposite trend was observed for CIP (EC₅₀ 95.9 and 15 mg L⁻¹, respectively). S. polyrhiza confirmed the remarkable sensitivity of aquatic plants to fluoroquinolones, with EC₅₀ values between 0.28 and 0.34 mg L⁻¹ depending on the endpoint considered. Notably, this species was also more sensitive to SMX than expected, with EC₅₀ values between 1.5 and 2.5 mg L⁻¹, which are an order of magnitude lower than those typically obtained with Lemna spp. exposed to sulphonamides. Considering the high environmental input of these antibiotics from both human and veterinary treatments, adverse effects on aquatic plants cannot be excluded, potentially leading to ecosystem-level consequences.