This study aimed to quantify, through a meta-analysis of literature data, average milk yield, milk composition and energy balance responses to changes in supply of: net energy (NE_L), metabolizable protein (MP), and their interaction, for dairy cows. Experiments with designs focused on the effects of protein and/or energy levels on milk performance were selected. The dietary NE_L and MP supplies were estimated for all treatments using the updated digestive model from INRA (Sauvant and Nozière, 2013). From all studies included in the database, 308 experiments (917 treatments) with experimentally induced variations in either NE_L or MP supplies were kept for this analysis. These treatments covered a wide range of diet characteristics and therefore a large part of the plausible NE_L and MP supplies that can be expected in practical situations. The average predicted MP supply was (mean ± SD) 2080 ± 467 g/d and average NE_L supply was 143 ± 25 MJ/d. The majority of those studies used multiparous Holstein-Friesian cows between 50 and 200 d in milk. Between and within-experiment variations were split to estimated milk responses. Linear and quadratic effects of NE_L and MP supplies and their interaction on milk responses were systematically tested, and removed from the model when non-significant (P > 0.05). Increasing either NE_L or MP supplies resulted in positive responses for milk, lactose, protein and fat yields. Interactions between NE_L and MP supplies were significant (P < 0.01) for milk yield, milk protein yield and milk lactose yield. Greater responses were found with increasing NE_L at higher MP supply, and vice versa. Energy balance was related, positively with NE_L supply, and negatively with MP supply. The negative interaction found between NE_L and MP supply diminished the effect of MP on energy balance at high NE_L supply. The current meta-analysis provides accurate estimation of milk yield (RMSE = 1.04 kg) and milk composition responses to change in supply of NE_L and MP. This study also found significant interactions between NE_L and MP supply for milk, protein and lactose yields.