Introduction: During intense exercise, splanchnic blood flow is reduced to enhance oxygen supply to peripheral tissue and maintain thermoregulatory control (Rowell 1974). Splanchnic hypoperfusion results in gut epithelia cell hypoxia and increases barrier injury, endotoxemia and gastrointestinal (GI) symptoms. Exercising in hypoxia can increase splanchnic hypoperfusion by 12-30% (Joyner & Casey 2014). Whether this exacerbates GI symptoms and injury is unclear. Intestinal fatty acid-binding protein (I-FABP) is a sensitive marker of epithelia injury within the small intestine. I-FABP appears in plasma rapidly after injury has occurred and has been shown to correlate with exercise-induced splanchnic hypoperfusion (van Wjick et al. 2011). The purpose of the present study was to investigate the impact of a single bout of submaximal treadmill running in normobaric-hypoxia on GI symptoms and I-FABP. Methods: Twelve well trained male runners performed two 1-hour bouts of treadmill exercise (85% gas exchange threshold) in a randomised order. One bout was performed in normoxia (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and the other in normobaric-hypoxia (HYP: (FIO2) = 14%). Plasma I-FABP was assessed pre-exercise, immediately post-exercise and 1 hour-post-exercise for the assessment of GI injury. Peripheral oxygen saturation (SpO2) was assessed from the forehead throughout each trial. Capillary samples were collected for the assessment of lactate every 15-mins, while heart rate (HR) and rating of perceived exertion (RPE) were recorded every 5-mins. Global gastrointestinal symptoms were collected at 15-min time points during treadmill exercise with all scores summed to give a total score (Pugh et al. 2017). A symptom specific GI questionnaire was completed following exercise (Gaskell et al. 2019). Physiological data were analysed using two-way (time x trial) repeated-measures ANOVA with Bonferroni adjusted post hoc tests where appropriate. Paired sample t-tests and Wilcoxon tests were used to analyse gastrointestinal symptom data.  Statistical significance was accepted at P < 0.05. Results: Global GI symptom scores collected during exercise and from the post-exercise questionnaire were higher during HYP compared to Norm (P < 0.05). The number of severe symptoms reported from the post-exercise questionnaire were also higher in HYP (1.5 ± 2.0) compared to NORM (0 ± 0) (P = 0.027). A two-way ANOVA revealed a time x trial interaction for I-FABP (P = 0.045), with higher concentrations immediately post-exercise in HYP when compared to NORM (1121.1 ± 438.7 vs 830.2 ± 422.3 pg/mL) (P = 0.008). Global gastrointestinal symptoms across both trials correlated with pre-post ∆I-FABP (P = 0.047). SpO2 was significantly lower at all time points in HYP, whereas lactate, HR and RPE were all higher in HYP when compared to NORM (P < 0.05). Conclusion: Taken together, our results indicate that submaximal treadmill exercise in normobaric-hypoxia causes more GI symptoms and intestinal injury than in normoxia. It is likely that the combination of reduced SpO2 and enhanced splanchnic hypoperfusion increased intestinal ischemia, causing greater injury during the HYP trial. The correlation of I-FABP and global GI symptoms was a novel finding and implies GI injury may partly be responsible for the onset of symptoms.