• To examine whether spousal responses to patient pain would alter the association between pain and patient health-related quality of life (HRQL), depression and disability. • Ninety-six women with IC/PBlS (mean age = 50.6 (13.8); mean time since diagnosis = 6.2 years) completed questionnaires on demographics, depressive symptoms (Center for Epidemiological Studies-Depression Scale), disability (Pain Disability Index), HRQL (Medical Outcomes Study Short Form 12) and a measure of perceived spousal responses to their pain (Multidimensional Pain Inventory). • A repeated measures multivariate analysis of variance examined association changes between pain and adjustment variables at high, moderate and low levels of negative, solicitous and distracting spousal responses. • The association between pain and all outcome variables did not vary as a function of levels of solicitous and negative spousal responses. • However, the association between pain and mental HRQL was stronger at lower levels (β=-1.25) of distracting responses than it was at moderate (β=-0.66) and higher (β=-0.06) levels. • Distracting spousal responses act to 'buffer' the deleterious effects of pain on mental HRQL for women suffering from IC/PBlS. Spousal support training may be a useful HRQL intervention.