Palm oil mill effluent (POME) contains high concentrations of biodegradable organic matter that require effective treatment before environmental discharge. Salinity can influence biological wastewater treatment performance; however, the operational response of POME treatment to different salinity conditions remains insufficiently understood. This study evaluated the performance of biological POME treatment under four salinity conditions (0, 6, 12, and 18 ppt) by assessing organic matter removal and nitrogen transformation. Treatment performance was evaluated based on chemical oxygen demand (COD), biological oxygen demand (BOD), COD/BOD biodegradability, specific degradation rate, ammonia removal, nitrite accumulation, and nitrate formation. The results showed that salinity influenced treatment performance, with 12 ppt producing the most favourable overall response among the tested conditions. The highest COD and BOD removal efficiencies were 94.41% and 94.87%, respectively, while the highest ammonia removal and nitrate concentration reached 89.2% and 17.6 mg L⁻¹, respectively. The initial COD/BOD ratios ranged from 2.19 to 2.45, confirming the high biodegradability of the POME. In contrast, the 18 ppt treatment showed lower organic matter removal and greater nitrite accumulation, indicating a less favourable nitrogen transformation response under the tested conditions. These findings demonstrate that salinity can be considered an important operational factor in biological POME treatment. Among the salinity levels evaluated, 12 ppt provided the most favourable balance between organic matter removal and nitrogen transformation, although further studies using a wider range of salinity levels, pilot-scale systems, and direct microbiological analyses are required to validate and refine this operational condition.