Water temperature is a major environmental factor afecting fsh activity, physiology, behavior, and growth. Alpha lipoic acid (ALA) has garnered much attention lately as an aqua feed supplement because of its antioxidant efects. Thus, this study aimed to assess the efect of dietary ALA on performance, hematological and immunological indices, behavior and oxidative stress, apoptosis, and genetic infammation in Oreochromis niloticus following 60 days of cold stress. Two hundred forty fsh were divided into four groups (15 fsh/replicate, N=60 fsh/group). The control (CNT) and ALA groups were reared at 25 °C and fed a basal diet without any supplementation or a basal diet containing 600 mg ALA/kg diet, respectively. The cold water-stressed group (CWS) and ALA+ CWS groups were reared at 18 °C and fed basal and basal diets containing ALA, respectively. The results revealed that dietary ALA supplementation signifcantly improved feed utilization and growth in fsh. ALA also mitigated CWS-induced microcytic hypochromic anemia and hyperlipidemia. Moreover, ALA supplementation considerably enhanced the antioxidant status and boosted intestinal α amylase, lipase, protease, and serum acetylcholinesterase activity of CWS-exposed fsh. Besides, ALA supplementation signifcantly reversed CWSinduced upregulation of proinfammatory genes, pro-apoptotic genes, heat shock protein, and proliferating cell nuclear antigen or downregulation of superoxide dismutase and catalase gene expressions in liver and spleen tissues. Furthermore, ALA supplementation reduced CWS-induced histopathological alterations in fsh liver, spleen, and intestine. We can conclude that ALA (600 mg/kg diet) could be recommended as an aqua feed supplement to boost growth, antioxidant capacity, and immunity and attenuate infammatory and apoptotic reactions of fsh reared under CWS-induced.