OBJECTIVE: The aim of this review was to investigate if exercise induced hypoalgesia (EIH) occurs following isometric muscle contraction in people with local musculoskeletal symptoms. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE, CINAHL & SportDiscus electronic databases were searched (inception to April 2020). ELIGIBILITY CRITERIA: Two authors independently evaluated eligibility. Randomised controlled and crossover (repeated measures) trials that measured the effects of isometric exercise in participants with localised musculoskeletal pain during, and up to 2 hours after isometric exercise were included. Other inclusion criteria included comparison to another intervention, or comparison to healthy controls. Primary outcomes were experimentally induced pain thresholds and secondary outcomes included measures of pain sensitivity from clinical testing. RESULTS: 13 studies with data from 346 participants were included for narrative synthesis. EIH was reported in some upper and lower limb studies but there were no consistent data to show isometric exercises were superior to comparison interventions. CONCLUSION: There was no consistent evidence for EIH following isometric exercise in people with musculoskeletal pain. These findings are different to those reported in asymptomatic populations (where EIH is consistently demonstrated) as well as conditions associated with widespread symptoms such as fibromyalgia (where isometric exercise may induce hyperalgesia). Although well tolerated when prescribed, isometric exercise did not induce EIH consistently for people seeking care for local musculoskeletal symptoms. The variance in the dose, location of contraction and intensity of protocols included in this review may explain the inconsistent findings. Further work is required to better understand endogenous analgesia in musculoskeletal pain conditions.