To determine whether acute exposure to simulated moderate altitude alters locomotor-respiratory coupling (LRC) patterns in runners, 13 trained male distance runners performed a running economy and maximal oxygen uptake (Vo2max) test in normoxia (NORM) and hypoxia (HYP) (FIO2= 15.8%; ~2,400 m/8,000 ft) on separate days. Running economy (RE), the degree of LRC, stride frequency-to-breathing frequency quotients (SF/fb), ratings of perceived exertion (RPE), and dyspnea were assessed at three common submaximal speeds and Vo2max. SF/fb were significantly lower at each submaximal speed in HYP (12.9 km/h: 2.91 ± 0.20 vs. 2.45 ± 0.17, 14.3 km/h: 2.53 ± 0.17 vs. 2.21 ± 0.14, 16.1 km/h: 2.22 ± 0.14 vs. 1.95 ± 0.09; P < 0.05). The degree of LRC (range: 36–99%) in HYP was not significantly different than NORM at any of the three common submaximal speeds. However, the degree of LRC was significantly higher at Vo2max in HYP than NORM (43.8 ± 3.4% vs. 57.1 ± 3.8%; P < 0.05). RE and RPE were similar at all running speeds. Dyspnea was significantly greater in HYP compared with NORM at 16.1 km/h (P < 0.05). Trained distance runners are able to maintain LRC in HYP, despite increases in breathing frequency. Within this unique population, years of training may enhance and optimize the ability to maintain LRC to minimize metabolic costs and dyspnea