Our objective was to determine effects of feeding calves pelleted starters with microbially enhanced (fungi-treated) soy protein (MSP) in replacement of soybean meal (SBM) with different milk replacers (MR). Thirty-six Holstein calves (2 d old; 24 females, 12 males) in individual hutches were used in a 12-wk randomized complete block design study. Treatments were (1) MSP pellets with MR formulated for accelerated growth (28% crude protein, 18% fat; MSPA), (2) SBM pellets with MR formulated for accelerated growth (SBMA), and (3) MSP pellets with conventional MR (20% crude protein, 20% fat; MSPC). Pellets were similar except for 23% MSP or 23% SBM (dry matter basis). Pellets and water were fed ad libitum throughout the study. Feeding rates of MR on a dry matter basis were 0.37kg twice daily during wk 1, 0.45kg twice daily during wk 2 to 5, and 0.45kg once daily during wk 6. Intakes were recorded daily. Body weights, frame size measurements, and jugular blood samples were collected 2 d every 2 wk at 3 h after the morning feeding. Fecal grab samples were collected 5 times per d for 3 d during wk 12 and then composited by calf for analysis of apparent total-tract digestibility of nutrients using acid detergent insoluble ash as an internal marker. Total and starter pellet dry matter intake were greatest for calves fed SBMA and least for MSPC. Calves had similar average daily gain among treatments, but there was a treatment by week interaction and during the last few weeks of the study calves on MSPC had less body weight compared with MSPA or SBMA. Gain-to-feed ratio was similar among treatments; however, there was a treatment by week interaction. Serum glucose was similar among treatments. Plasma urea nitrogen was greatest for calves fed MSPA and least for MSPC. Plasma concentrations of IGF-1 were greatest for calves fed SBMA. Plasma concentrations of triglycerides were greatest for calves fed MSPC. Plasma concentrations of β-hydroxybutyrate had a treatment by time interaction. Treatments had similar total-tract dry matter digestibility, but calves fed MSPC had greater crude protein digestibility than SBMA, with MSPA similar to both. Results demonstrated calves fed pelleted starters with MSP had maintained growth performance with less starter intake compared with SBM.