Twenty eight lactating buffaloes in the 2^nd to the 5^th lactating season, weighing 500-600 kg were used after one week of calving in a completely randomized design with 2×2 factorial arrangement of treatments to evaluate the effect of varying levels of protein and energy on nutrient intake, digestibility, milk yield, feed conversion and economic efficiency. The low and high protein diets (12 and 16% CP) and low and high energy diets (60 and 65% total digestible nutrients, TDN) were used in four experimental diets include low protein–low energy (LP-LE), low protein–high energy (LP-HE), high protein–low energy (HP-LE) and high protein–high energy (HP-HE). Results showed that the CP digestibility and digestible crude protein (DCP) values were increased (P<0.05) in high protein diet. While, the digestibility coefficients of either extract (EE) and nitrogen free extract (NFE) and TDN values were increased (P<0.05), but crude fiber (CF) digestibility decreased (P<0.05) in high energy diet. The HP-HE diet recorded the highest digestibility coefficients of CP, EE and NFE and nutritive values and HP-LE diet had the highest CF digestibility (P<0.05). Dietary DCP intake increased (P<0.05) in high protein diet and the intake of DM and TDN increased (P<0.05) in high energy diet. The HP-HE diet showed (P<0.05) the highest intake of TDN and DCP. The yield of actual milk and 7% fat corrected milk (FCM) increased (P<0.05) in high protein and high energy diet (HP-HE). The contents of protein, SNF and TS in milk increased (P<0.05) in high protein diet. While, the contents of protein, lactose, SNF and ash in milk increased (P<0.05) and fat decreased (P<0.05) in high energy diet. The HP-HE diet revealed the highest milk protein, lactose, SNF and TS contents and HP-LE diet had the highest fat content (P<0.05). The amounts of DM and TDN per kg 7% FCM decreased (P<0.05), but the amount of DCP per kg 7% FCM increased (P<0.05) in high protein diet. While, the amounts of DM, TDN and DCP per kg 7% FCM decreased (P<0.05) in high energy diet. The HP-HE diet showed the lowest amounts of DM and TDN per kg 7% FCM and LP-HE diet had the lowest amount of DCP per kg 7% FCM (P<0.05). Average daily feed cost and total revenue increased (P<0.05) in high protein diet. While, average daily feed cost and feed cost per kg 7% FCM decreased (P<0.05), but total revenue and economic efficiency increased (P<0.05) in high energy diet. The LP-HE diet recorded the lowest average daily feed cost, while HP-HE diet showed the lowest feed cost/kg 7% FCM and the highest total revenue and economic efficiency (P<0.05). Dietary protein level not affected postpartum reproductive performance of lactating buffaloes (P>0.05). However, the periods from parturition to first estrus and first service, service period, days open and number of services per conception decreased (P<0.05), but conception rate increased (P<0.05) in high energy diet. Moreover, buffaloes fed HP-HE diet showed the short periods from parturition to first estrus and first service, service period, days open, the lowest number of services per conception and the highest conception rate (P<0.05).