Present study was designed to decipher the haemato-biochemical and hormonal profile following bypass nutrient supplementation in Murrah buffaloes during early lactation. Forty Murrah buffaloes just after parturition divided randomly into four equal groups and fed basal diet constituting common green fodder and wheat straw, while two different types of concentrates mixture (CM) having 25 (CM1, for group fed control or bypass fat, BPF diet) and 40 percent (CM2 for group fed bypass protein, BPP and BPP with BPF, BPPF diet) of BPP using variable feed ingredients in CM. Animals of group BPF and BPPF additionally fed 15 g bypass fat (long chain fatty acid of calcium salt) for each kg of milk produced for initial 90 days of lactation. Blood sampling was carried out at 0 day (before starting supplementation) and thereafter at an interval of one month, till 120th day after parturition, to find out the effect of supplementation as well is after effects. Significant reduction (P LT 0.05) in serum urea on day 60 was observed in bypass protein fed groups (BPP and BPPF) remains indicative of efficient nitrogen utilization. Thus overall mean total protein in bypass protein fed groups (BPP and BPPF) was higher (P LT 0.05) than control group. Values of albumin also on day 90 (P LT 0.01), 120 (P LT 0.05) as well as overall mean remained higher (P LT 0.001) in group fed CM high in rumen protected protein (BPP and BPPF) than groups fed low bypass protein CM (control and BPF). Supplementation of BPPF improved (P LT 0.05) overall mean cholesterol level as compared to control. Reduction (P LT 0.05) in low density lipoprotein values was observed on day 60 in BPF group as compared to others, while overall mean high density lipoprotein (HDL) in bypass protein fed groups (BPP and BPPF) was found to be higher (P LT 0.01) as compared to others. IGF-1and BHBA showed non-significant difference in all treated groups at different intervals in addition of haematological parameters. It may be concluded that feeding of bypass protein (BPP and BPPF) improved serum overall total protein, albumin, cholesterol and HDL in post-parturient Murrah buffaloes during early lactation.