The objective of the current study was to find out the independent and interactive effects of prilled fat supplementation with protein on the production performance of early lactating Nili Ravi buffaloes. Sixteen early lactating buffaloes (36.75±5.79 d in milk; mean±standard error) received 4 treatments in 4×4 Latin-square design according to 2×2 factorial arrangements. The dietary treatments were: i) low protein low fat, ii) low protein high fat, iii) high protein low fat, and iv) high protein high fat. The dietary treatments contained 2 protein (8.7% and 11.7% crude protein) and fat levels (2.6% and 4.6% ether extract) on a dry matter basis. The yields of milk and fat increased with increasing protein and fat independently (p≤0.05). Energy-, protein-, and fat-corrected milk yields also increased with increasing protein and fat independently (p≤0.05). Increasing dietary protein increased the protein yield by 3.75% and lactose yield by 3.15% and increasing dietary fat supplies increased the fat contents by 3.93% (p≤0.05). Milk yield and fat-corrected milk to dry matter intake ratios were increased at high protein and high fat levels (p≤0.05). Milk nitrogen efficiency was unaffected by dietary fat (p>0.10), whereas it decreased with increasing protein supplies (p≤0.05). Plasma urea nitrogen and cholesterol were increased by increasing protein and fat levels, respectively (p≤0.05). The values of predicted methane production reduced with increasing dietary protein and fat. It is concluded that prilled fat and protein supplies increased milk and fat yield along with increased ratios of milk yield and fat-corrected milk yields to dry matter intake. However, no interaction was observed between prilled fat and protein supplementation for production parameters, body weight, body condition score and blood metabolites. Predicted methane production decreased with increasing protein and fat levels.