This study aimed to investigate the effects of 6 wk oral supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate (HMBCr) on indices of health in highly trained athletes. Elite, male rugby league players (n=28) were allocated to 1 of 3 groups: a control group (n=6), a HMB group (3 g/d; n=11), or a HMBCr group (3 g/day HMB, 3 g/d Cr; n=11). Testing prior to, and immediately following, supplementation included a full blood count, plasma testosterone and cortisol, blood electrolytes, lipids, urea and glucose, sperm count and motility, and assessment of psychological state. A 3 x 2 factorial ANOVA revealed no effect of HMB or HMBCr on any of the measured parameters except minor changes in blood bicarbonate and blood monocyte and lymphocyte counts. Blood bicarbonate was significantly decreased in the HMB post-supplementation sample compared to the control and HMBCr groups. Blood monocyte and lymphocyte counts showed no within-group changes for HMB or HMBCr supplementation but were significantly different from the control. However, the majority of these readings remained within normal range. HMB and HMBCr were concluded to have no adverse effects on the parameters evaluated in this study when taken orally by highly trained male athletes over a 6-wk period.