To explore possible associations between self-reported prevalence of catastrophic illnesses such as chronic renal failure, HIV/AIDS and cancer and a set of structural social determinants.Ecological study using data from the 2005 Population Census conducted by the National Administrative Department of Statistics (DANE), focusing on municipalities in the Colombian department of Valle del Cauca that experienced the highest prevalence rates for catastrophic illnesses during 2000-2005. Associations were measured with Pearson's chi-squared statistic and Fisher's Exact Test. Prevalence ratios were calculated, with 95% confidence intervals.Statistically significant associations were observed between catastrophic illnesses and social structural determinants in the form of illiteracy, deficient sanitary infrastructure, quality of housing units and access to health services.A role was observed for social determination of catastrophic illnesses in this context. However, additional analyses are required that recognize the complexity of health-determining processes and that explore the interrelationships among social, structural, behavioral and psychosocial determinants in depth.