BACKGROUND Offset analgesia (OA) and conditioned pain modulation (CPM) are frequently used paradigms to assess the descending pain modulation system. Recently, it was shown that both paradigms are reduced in chronic pain, but the influence of acute pain has not yet been adequately examined. OBJECTIVE The aim of this study is to investigate OA and CPM after exercise-induced pain to evaluate whether these tests can be influenced by delayed-onset muscle soreness (DOMS) at a local or remote body site. METHODS Forty-two healthy adults were invited to 3 separate examination days: a baseline appointment, the consecutive day, and 7 days later. Participants were randomly divided into a rest (n = 21) and an exercise group (n = 21). The latter performed a single intensive exercise for the lower back. Before, immediately after, and on the following examination days, OA and CPM were measured at the forearm and the lower back by blinded assessor. RESULTS The exercise provoked a moderate pain perception and a mild delayed-onset muscle soreness on the following day. Repeated-measurements analysis of variance showed no statistically significant main effect for either OA or CPM at the forearm or lower back (P > 0.05). CONCLUSIONS Delayed-onset muscle soreness was shown to have no effect on the inhibitory pain modulation system neither locally (at the painful body part), nor remotely. Thus, OA and CPM are robust test paradigms that probably require more intense, different, or prolonged pain to be modulated.