Intensive livestock farming has increased the use of veterinary pharmaceuticals in many developing countries, and this is considered a significant concern to the freshwater ecosystem. However, the information on the potential acute toxicity of piggery effluent waste and the veterinary pharmaceutical effluent discharged into the aquatic environment is limited. This study assessed the adverse effect of a piggery effluent and the cocktail mixtures of high- and low-level doses of three frequently occurring veterinary pharmaceuticals (tetracycline (TETR), ivermectin (IVER), and salicylic acid (SALA)) on freshwater organisms using three representative freshwater biotests organisms: Pseudokirchneriella subcapitata (P. subcapitata), Daphnia magna (D. magna), and Tetrahymena thermophila (T. thermophila). The freshwater organism test results showed that the 24-h and 48-h EC₅₀ algal toxicity to P. subcapitata exposed to 10% unfiltered piggery effluent were 25.6 and 49.3% respectively while the 24-h LC₅₀ value to Cladocera, D. magna exposed to unfiltered piggery effluent was 23.2 (17.7–30.4)%. The 24-h EC₅₀ protozoan toxicity to T. thermophila exposed to 1% HLD veterinary pharmaceuticals was 0.014 μg/L. Thus, the study established the different sensitivities of freshwater organisms to various percentage levels of piggery effluent and high- and low-level doses of veterinary pharmaceutical. The piggery effluent and the pharmaceutical cocktail mixtures have potential toxicological effects on the freshwater ecosystem.