Purpose It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise-heat-stress, which in-turn may increase the risk of exertional heat illness (EHI). We examined heat strain during exercise-heat-stress 30 min after EIMD to coincide with increases in circulating pyrogens (eg interleukin (IL)-6) and 24 h after EIMD to coincide with the delayed muscle inflammatory response when a higher rate of metabolic energy expenditure (Mx), and thus decreased economy, might also increase heat strain. Methods Thirteen non-heat-acclimated males (mean (SD), age 20 (2) years) performed exercise-heat-stress tests (running for 40 min at 65% VO2max in 33 C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment involving running for 60 min at 65% VO2max on either-10% gradient (EIMD), or+ 1% gradient (CON) in a cross-over design. Rectal (Tre) and skin (Tsk) temperature, local sweating rate and Mx were measured throughout HS tests. Results Compared with CON, EIMD evoked higher circulating IL-6 pre-HS1 (P< 0.01) and greater plasma creatine kinase and muscle soreness pre-HS2 (P< 0.01). The ΔTre was greater following EIMD than CON during HS1 (0.35 C, 95% CI 0.11-0.58 C, P< 0.01) and HS2 (0.17 C, 95% CI 0.07-0.28 C, P< 0.01). Mx was higher on EIMD throughout HS1 and HS2 (P< 0.001). Thermoeffector responses (Tsk, sweating rate) were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25 min during HS1 (P< 0.05). The final Tre during HS1 correlated with the pre-HS1 circulating IL-6 concentration (r= 0.67). Conclusion Heat strain was increased during endurance exercise in the heat conducted 30min after and, to a much lesser extent, 24h after muscle-damaging exercise. These data indicate that EIMD is a likely risk factor for EHI particularly during exercise-heatstress when behavioral thermoregulation cues are ignored.