Salinity is a known factor in shaping population dynamics and community structure through direct and indirect effects on aquatic ecosystems. Salinity changes further influence food webs through competition and predation. The responses of Moina macrocopa (Cladocera) collected from Setiu Wetland lagoon (Terengganu) was evaluated through manipulative laboratory experiments to understand the ability of M. macrocopa to tolerate high salinity stress. Specifically, the fatty acid composition, growth, survival, and reproduction of this cladocerans species was examined. Sodium chloride (NaCl) as used in the treatments water with the concentration 0, 4, 6, 8, 12, and 15 salinity. Fatty acid levels were determined using Gas Chromatography and Mass Spectrophotometry (GC-MS). The results indicated that optimal conditions produced the highest fatty acid content, especially the polyunsaturated fatty acid content, such as EPA (eicosapentaenoic acid), ALA (alpha-linoleic acid), ARA (arachidonic acid), and DHA (docosahexaenoic acid). Furthermore, M. macrocopa survival was best at salinity 0, with a percentage of 98%, whereas the opposite occurred at salinity 15, with approximately 20% of viable animals surviving. Besides, M. macrocopa also showed the highest reproduction rate at salinity 0 (e.g., average initial age of reproduction, 4.33 ± 0.58 days) compared with other salinities level. Interestingly, the difference in growth at different salinities was not evident, an unusual finding when considering adverse effects such as osmoregulation pressure on the organism. Based on the results, we conclude that M. macrocopa can only tolerate salinity below salinity 8 and cannot withstand stressful environmental conditions associated with salinities above 8.