Fish are continuously exposed to multiple environmental stressors that work cumulatively and synergistically. This study assessed the stress responses of Indian major carps (IMCs) cultured in a sewage-fed pond (SP) in the East Kolkata Wetland (EKW), India and compared with the normal carps in situ. The experiment was conducted in two farms that cultured Labeo rohita, Catla catla and Cirrhinus mrigala for seven months, covering the summer and winter periods. Serum biomarkers of primary (cortisol) and secondary (glucose, total protein, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)) stress responses, and oxidative stress (superoxide dismutase (SOD)) were quantified using standard kits. The health status of carps was evaluated as a tertiary response. The biological oxygen demand, hardness, total dissolved solids, ammonia and phosphate levels of both ponds exhibited marked variations. The SP carps had significantly low haemoglobin and total protein, and high serum glucose, creatinine, ALT, AST and LDH levels. The SOD and cortisol levels were comparatively low in SP carps. The winter temperature had a significant effect on serum glucose, cortisol, SOD, creatinine, ALT and AST. Carps had a high degree of ectoparasitic infestation during the winter. Cirrhinus mrigala of the SP had significantly high serum creatinine levels. The increasing levels of serum glucose, creatinine, ALT and AST suggested that these indices, which were more pronounced in the carps of EKW in conjunction with winter temperature, could be useful biomarkers of stress, kidney and liver functioning in carps, respectively.