Milk protein concentrates are increasingly used as enrichment ingredients in cheese manufacturing. Ultrafiltration (UF) membranes with a molecular weight cut-off of 10 kDa are typically used for concentrating skim milk proteins content up to 57 to 84% (dry basis). However, some operating parameters such as transmembrane pressure control, temperature or multistage design have important impacts on process efficiency and functional properties of the concentrates. The objective of this work was to investigate the effect of transmembrane pressure (TMP) on the membrane performance and the protein retention by UF on skim milk using a 10 kDa polyethersulfone membrane. Skim milk was concentrated by a 4X volumic concentration factor at 50°C. Three operating modes were investigated: constant transmembrane pressure, 90 and 53 psi, and constant flux. Fouling of the membrane system was characterized using the resistance-in-series approach. It was found that operating at constant flux increases (P < 0.05) the reversible fouling and consequently increases the energy requirement necessary to produce milk concentrate in comparison with to operating at lower constant transmembrane pressure. Our results showed that transmembrane pressure control does not affect the irreversible fouling during milk protein concentrate production, 66.5 ± 0.6% protein. Also, the protein retention was not affected (P < 0.05) by changes in transmembrane pressure. This study demonstrates that milk protein concentration by UF at low transmembrane pressures limits the formation of cake layer (reversible fouling) and this improves the efficiency of the process by reducing the energy consumption during filtration and its environmental footprint.