Weaning is a stressful event associated with lowered growth rates during weaning and potentially post-weaning. Early weaning, particularly from a high volume of milk could exacerbate those growth depressions as the calves would take a longer time to achieve a desired starter intake. This study was conducted to examine the effects of l-glutamine supplementation (2.0% of total DM intake) during weaning on starter intake, growth, and health of Holstein heifer calves weaned early from a high volume of milk. Thirty-six Holstein heifer calves of 28 d of age, were assigned to 3 treatments (n = 12), 1) a later weaning age of 49 d (LW), 2) an early weaning age of 35 d (EW), and 3) the early weaning age supplemented with l-glutamine (EW+Gln). Calves of EW+Gln group received l-glutamine in milk 1 wk before and 1 wk after weaning has begun by reducing milk allowance from 9.0 to 3.0 L/d. Calves were completely weaned once they achieved a 1.0 kg/d starter intake. Body weight, hip height, hip width (HW) and body length (BL) were measured weekly. Blood (jugular) was drawn and analyzed for serum haptoglobin (HPT) concentration during the first week of weaning. Treatment effects were analyzed using linear mixed-effect models including fixed effects of treatment, and parity of the dam, and random effect of calf. Calves of EW+Gln group had greater average daily gain (ADG, 0.2 kg/d, P = 0.011) during the first week of weaning as opposed to EWs. Moreover, EW+Gln took fewer number of days to achieve a starter intake of 1.0 kg/d (15 vs. 17 d, P < 0.01), and thus weaned completely at a younger age than EW. Besides, EW+Gln had numerically lower (1.04 vs. 1.78 g/L, P = 0.225) serum HPT concentrations during weaning, and greater HW (P = 0.014) and BL (P = 0.054) post-weaning (70 d). Meanwhile, LW were weaned completely at 59 d of age and had BW, ADG, and starter intake similar to that of the early-weaned calves post-weaning (70 d). It could be possible to wean calves from a high milk volume as early as 5 wk of age without compromising growth performance and starter intake post-weaning. Supplementation of l-glutamine could help calves withstand weaning stress successfully as reflected by improved ADG and starter intake during weaning.