The aim of this study was to examine the efficacy of meloxicam (MEL) as supportive therapy for calves with neonatal calf diarrhea complex. For this double-blind controlled trial, 62 Holstein male calves were purchased at birth and transported to a research facility. At the naturally occurring onset of diarrhea, defined as the first occurrence of a fecal score greater than 2 on a 4-point scale, calves were enrolled in the study. Each calf with diarrhea was randomly assigned to receive a single subcutaneous injection of MEL at a rate of 0.5 mg/kg of BW or an equal volume of placebo (PLA) solution. Milk, starter ration, and water intakes were determined daily for each calf from arrival until 56 d of age. The calves were weighed on arrival and each week thereafter. Time to weaning and weaning weight were recorded for each calf. Crude associations between treatment and each outcome variable were examined using t-tests and Pearson chi-squared tests. Subsequently, multivariable regression models were constructed to examine the impact of MEL therapy on meaningful outcome variables. The primary experimental unit in all analyses was the individual calf. In total, 56 calves presented with clinical signs of diarrhea and were enrolled in the study. Two PLA-treated calves died after being enrolled in the study, and there was no calf mortality among the MEL-treated calves. For calves that developed diarrhea after 10 d of age, MEL-treated calves were more likely to consume their entire daily milk allowance (P 0.05), but MEL-treated calves tended to wean earlier (P = 0.11) than PLA-treated calves. These results demonstrate that calves receiving a single injection of MEL at the onset of diarrhea had improved appetite and performance compared with PLA-treated calves. Thus, MEL is an effective supportive therapy for neonatal calf diarrhea complex.