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Unlabelled: This double-blind, placebo-controlled, repeated-measures experiment examined the effects of a 5 mg . kg(-1) body weight dose of caffeine on delayed-onset muscle pain intensity and force loss in response to 64 eccentric actions of the dominant quadriceps induced by electrical stimulation. Low caffeine-consuming college-aged females (n = 9) ingested caffeine or placebo 24 and 48 hours following electrically stimulated eccentric exercise of the quadriceps. One hour after ingestion, maximal voluntary isometric contractions (MVIC) and submaximal voluntary eccentric actions were used to determine force loss during activation of damaged quadriceps and whether caffeine attenuates muscle pain intensity. Pain intensity was measured using a 0 to 100 visual analog scale. Caffeine produced a large (12.7 raw visual analog scale [VAS] units; -48%; Cohen's d effect size = -0.88), statistically significant hypoalgesia during the MVIC (t = -2.52; df = 8; P = .036). The reduction in pain scores during submaximal voluntary eccentric movements was smaller (7.8 raw VAS units; -26%, d = -0.34), as was the increase in MVIC force (4.4%; d = 0.13)., Perspective: Eccentric exercise occurs when skeletal muscles produce force while being lengthened. For example, the biceps brachii muscles act eccentrically when a cup of coffee is lowered from the mouth to a tabletop. This experiment found that caffeine (equal to approximately 2 cups of brewed coffee) could produce a large reduction in pain resulting from eccentric exercise-induced, delayed-onset muscle injury. This finding may improve the quality of life of individuals who experience skeletal muscle pain after engaging in unaccustomed, eccentrically biased exercise.