The use of milk replacer instead of whole milk may be an economical alternative to calf-rearing systems. However, together with the volume fed, its composition is critical for high performance, especially regarding the origin of the protein. Two milk replacers with different protein content were evaluated to see the effect on the performance of calves. Thirtythree Holstein calves were distributed in the treatments: (1) High Volume and Low Protein (HV/LP), control group: 8 liters, 19.5% CP; (2) High volume and high protein (HV/HP): 8 liters, 23.7% CP and (3) Low Volume and High Protein (LV/HP): 6 liters, 23.7% CP. Calves were gradually weaned from the seventh week of life. Starter feed intake and fecal score were recorded daily. Weekly, calves were weighed, body measurements taken and blood samples were collected for metabolites analysis. Fecal score was lower (P>0.05) for animals in treatments HV/LP. Animals in treatments HV/HP had greater number of days in diarrhea (P<0.05) as compared to LV/HP fed calves. However LV/HP fed calves presented 66.7% mortality rate with a lower average age at death (P<0.05). There was no effect of treatments for body weight, average daily gain, body measurements and intake (P>0.05). Regarding blood metabolites, lactate concentration was higher (P<0.05) in animals fed HV/HP as compared to LV/HP and total protein concentration was lower (P<0.05) for calves fed HV/HP, while the other metabolic parameters did not differ. The use of substitutes with high vegetable protein content negatively affects the performance of calves and may increase mortality rates when low volumes are fed.