One-hundred seven (2–5 d old) individually fed Holstein heifer calves (39.8 ± 0.70kg) were randomly assigned to 1 of 4 treatments to evaluate pre- (d 1–42) and post weaning (d 43–56) calf performance and health when fed milk replacers (MR) with alternative protein sources. The study was conducted between February and April, 2014. Calves were assigned to non-medicated 24% CP:20% fat MR with (1) All milk protein, (2) 25% of total protein from plasma, (3) 25% of total protein from plant peptide proteins, or (4) 12.5% plasma,12.5% peptide proteins. All calves were fed a non-medicated 24% CP:20% fat MR at 0.34 kg in 2.39 L water (12.5% solids) 2× daily for the first 35 d and 1× daily d 36 to weaning at 42 d. Day 1 to 14, 1:1 neomycin:oxytetracycline was added to the MR solution to provide 22 mg/kg BW/d. Calf starter (CS; 18% CP as-fed) and water were fed free choice from d1. Milk replacer feeding rate was adjusted if ambient temperatures taken 0800 h were −23.3 to −28.3°C (+ 20% volume) or > −28.9°C (+ 40% volume). During the study, average minimum temperatures were - 21.1, - 9.6 and 0.6°C for February (22 d < −17.8°C), March (3 d < −17.8°C) and April respectively. There were no pre- or post weaning ADG differences (P > 0.05). Calves averaged 0.73 kg/d gain for the 56-d study. Milk replacer intake was similar for all treatments, averaging 25.1 kg. There were no differences (P > 0.05) in CS or total DMI intake which averaged 51.5 and 76.7 kg for the 56-d study, respectively. There were no differences in pre- and post weaning gain/feed. Gain/feed averaged 0.58 kg for the 56 d study. Across treatments, calves doubled their initial BW and gained an average of 11.7 cm in frame growth. There were no differences in number of scouring d pre- and post weaning and health treatment costs. Under the conditions of this study, replacing 25% of the total milk protein in MR with alternative sources resulted in calf performance and health similar to those fed an all milk protein MR.