This study aims to determine the impact of musculoskeletal pain (in terms of intensity of the pain, location and functional disability due to back pain) and other factors (socio-demographic, lifestyle and co-morbidity) on the health-related quality of life on a group of shellfish gatherers. This observational transversal study included 929 shellfish gatherers (18-69 years, 98.7 % women) who completed a self-administered questionnaire, including socio-demographic and lifestyle questions, co-morbidity, intensity and location of musculoskeletal pain, and Roland-Morris Disability Questionnaire (RMDQ). Health-related quality of life was assessed using the 36-item Short Form Survey (SF-36). Physical component summary (PCS) and mental component summary (MCS) of the SF-36 were considered as outcome variables. The impact of the different factors on the PCS and MCS scores was evaluated using a stepwise linear regression analysis. Physical health was found to be independently associated to intensity of musculoskeletal pain (regression coefficient, B = -0.96), number of locations with musculoskeletal pain (MSP) (B = -0.77), presence of pain in the hip-knee (B = -2.26), self-reported rheumatic disorders (B = -2.79), lower back pain (B = -1.62) and age (B = -0.06). Mental health was associated with the presence of self-reported depressive syndrome (B = -1043.1) and RMDQ score (B = -42.2). The sample had significantly lower values than the reference population in all of the dimensions of the SF-36. Intensity of the pain, pain in the hip-knee, lower back pain, functional disability due to back pain and number of locations with musculoskeletal pain were found to have a detrimental impact on the physical health of the workers. Depressive syndrome and greater functional disability due to back pain, in turn, predict worse mental health.