The present study was conducted to evaluate the effect of commercial exogenous fibrolytic enzyme (EFE) mixture added at 1.5 and 3.0 g (cellulase 4,000 microM glucose/g/h + xylanase 7,990 microM xylose/g/min; 50:50 w/w) per kilogram of dry matter (DM) of feed on nutrient digestibility, milk production, milk composition, and some blood constituents in lactating Murrah buffaloes. Eighteen buffaloes were allotted to three dietary treatments, on the basis of milk yield (8.48, 8.52, and 8.53 kg/day) and days in lactation (68.5, 80.33, and 82.00) for 90 days. The buffaloes were fed a total mixed ration (TMR) comprising of 45% chaffed wheat straw, 15% chopped green maize, and 40% concentrate on DM basis (control group), the same TMR plus EFE at 1.5 g/kg DM (T-1 group) and the same TMR plus EFE at 3.0 g/kg DM (T-2 group) supplemented through the concentrate mixture. There was no effect of fortifying EFE mixture on DM intake and crude protein intake (grams per day) whereas total digestible nutrients intake (kilogram per day) was higher by (P < 0.05) 12.53% in T-1 group over that of control, and there was no significant difference between T-2 and control groups. The average daily milk yield and 4% fat-corrected milk (FCM) yield was higher (P < 0.05) by 12.99% and 15.17% in T-1 group as over that of control, and there was no difference between T-2 and control groups. There was no (P > 0.05) difference in blood glucose and blood urea nitrogen concentration in different experimental groups. It is concluded that supplementation of cellulase and xylanase mixture at 1.5 g/kg of DM of TMR containing wheat straw (45%), green maize (15%), and concentrate (40%) on DM basis significantly increased (P < 0.05) the average daily milk yield and FCM yield in Murrah buffaloes due to improved dietary fiber digestion.