The current study examined the relationship between illness invalidation and shame in a sample of 168 adults with myalgic encephalomyelitis/chronic fatigue syndrome. Based on review of existing qualitative research, it was hypothesized that there would be a significant positive relationship between perceived illness invalidation and experiences of state shame. Additionally, in light of the Stress Buffering Model, it was hypothesized that perceived social support would moderate the relationship between illness invalidation and shame. Results indicated that illness invalidation in the form of lack of understanding significantly correlated with experiences of shame. Hierarchical multiple regression revealed that perceived social support did not, however, significantly moderate the relationship between state shame and illness invalidation in the form of lack of understanding.