The present study was designed to assess the interrelationship between hematological, serum biochemical, and endocrinological profiles and oxidative stress markers and lactational stages in crossbred (CB) dairy cows of Andaman and Nicobar Islands (ANI). Healthy (n = 6) CB cows (50-62.50% exotic inheritance; Holstein Friesian × Andaman local) of 4th parity with age of 7-9years and body weight of 350-400kg were selected from Cattle Breeding Farm, ICAR-Central Island Agricultural Research Institute (ICAR-CIARI), Port Blair, ANI. These experimental cows were synchronized with Ovsynch protocol, and parturition was planned to happen in the month of May-June. Lactation was allowed for 305days. Hematological profiles, serum biochemical profiles, oxidative stress markers and endocrinological profiles were measured at a 15-day interval from day 07 to 305 of lactation (after 6days of colostrum). The lactation period was divided into first (day 07 to 90), second (day 91 to 180), and third (day 181 to 305) stage of lactation. Average daily milk yield (L) did not vary among the stages of lactations; however, first (8.56 ± 1.26) and second (9.79 ± 0.87) stages had higher milk yield compared to third (7.93 ± 0.79) stage of lactation. Hematological profiles did not vary among the stages of lactation; however, these values were within the range of bovine species at lactation. Serum glucose, triglyceride, total cholesterol, total protein, globulin, and blood urea nitrogen (BUN) increased (P < 0.05) and albumin and creatinine decreased (P < 0.05) gradually as lactation stages advanced. Activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and concentration of calcium, phosphorous, and magnesium were nearly similar among the stages of lactation. Similarly, triiodothyronine (T3), and thyroxine (T4) increased and prolactin and cortisol decreased (P < 0.05) gradually as stages of lactation advanced. Total antioxidant capacity (TAC) increased and malondialdehyde (MDA) decreased (P < 0.05) as lactation stages advanced. The results of the present study indicated that the lactating CB cows suffered nutritional stress (deficiency of protein, carbohydrate, lipids, and minerals), physiological stress (higher cortisol), oxidative stress (higher MDA and deficiency of total antioxidant capacity), and hormonal imbalance (higher prolactin and cortisol and deficiency of thyroid hormones) during the early stages of lactation. Thus, the first and second stages are more stressful events compared to the third stage of lactation in the CB cows in ANI. Therefore, regular monitoring of blood components and accordingly suitable feeding strategies with balanced nutrients and minerals, supplementation of suitable antioxidants, and appropriate management practices need to be implemented to mitigate these stresses and to prevent metabolic disorders with maximum milk production during different stages of lactation in CB cows under humid tropical island ecosystem of Andaman and Nicobar Islands.