Objectives: Neopterin has been used as a stress marker in team sport athletes, but its use in monitoring stress in hypoxic training requires further investigation. The objective of this study was to determine whether neopterin measures could detect differences between hypoxic and normoxic training stress and whether such levels could predict subsequent performance. Methods: Nineteen amateur club rugby players completed two repeated sprint (cycling) sessions per week for 3 weeks in either hypoxic (RSH, n = 9, FIO2 = 0.145) or normoxic (RSN, n = 10, FIO2 = 0.209) conditions. Repeated sprint ability (RSA, running), and the Yo-Yo Intermittent Recovery Level 1 test (YYIR1) were assessed pre-and post-intervention. Resting neopterin, total neopterin, and the difference between resting and post-exercise neopterin and total neopterin levels (acute change) were monitored during training. Results: Neopterin and total neopterin measurements demonstrated high individual variability in all participants. Neopterin and total neopterin were likely and very likely elevated respectively in RSH vs RSN between weeks 1 and 3 (neopterin, 56.4 %, ± 55.6, p = 0.10; percent change, ± 90% confidence interval, p value; total neopterin, 42.2 %, ± 23.5, p = 0.02). Aside from a moderate correlation between the acute change in total neopterin with YYIR1 (r = -0.38) there were no substantial correlations between neopterin and total neopterin measures and post-intervention performance. Conclusions: Neopterin or total neopterin can distinguish between hypoxic and normoxic training. However, high individual variability and limited predictive ability of subsequent performance may restrict the practical application of this stress marker.