Immediate exercise-induced pain (IEIP) and DOMS are types of exercise-induced pain, known as barriers to exercise, especially in conditions like chronic fatigue and fibromyalgia. IEIP occurs during, whereas DOMS days after exercise, and are attributed to metabolites and inflammation in muscle, respectively. Acid sensing ion channels (ASICs), expressed in muscle afferents, play role in different pain conditions. ASICs are activated by H+ and chemicals released during exercise and microinjuries. Recently, we showed ASICs are required for IEIP. Here, we tested if ASICs are also required for DOMS. Wild type (WT) and ASIC3-/- mice underwent an exhaustive exercise, or were sedentary (control group). Muscle pain was assessed by muscle withdrawal threshold (MWT) at baseline, immediately and 24h after exercise. Locomotor movement, grip strength and exercise performance were tested at baseline and 24h after exercise for WT and ASIC3-/- to evaluate DOMS. ASIC3-/- had similar baseline muscle pain, locomotor activity, grip strength, and exercise performance as WT. WT showed diminished MWT immediately after exercise indicated they developed IEIP (P<0.001), but ASIC3-/- mice did not (also no difference in lactate after exercise). However, both, ASIC3-/- and WT had similarly lower MWT and grip strength (P<0.01) 24h after baseline-exercise, nevertheless, ASIC3-/- displayed significantly lower locomotor activity and repeat exercise performance at 24h time-point compared to WT (P<0.05). While WT and ASIC3-/- had a same exercise performance, they had different pain perception immediately after, but not a day after exercise. Unlike WT mice, ASIC3-/- did not develop IEIP. At 24h after exercise, ASIC3-/- developed similar DOMS features (hyperalgesia and lower strength) as WT. Interestingly, ASIC3-/- mice had diminished locomotor movement and repeated exercise performance at 24h. These results show ASICs are required for IEIP, but not DOMS, and they might play a protective role from muscle injury during metabolic perturbation conditions like inflammation and exercise. Grant support from the Department of Veterans Affairs Merit Award (5I01BX000776).