Theories applied to work stress predict that coping will mediate and support will moderate the impact of work demands on worker well-being. We explored the mediating and moderating effects of coping and support on the relationship between perceived work demands and burnout in support staff working with adults with intellectual disabilities. Ninety-six support staff completed questionnaires that measured demographic factors, perceived work demands, coping, support, and burnout. A sub-sample participated in a follow-up 22 months later. Cross-sectional regression analyses revealed a relationship between work demands and emotional exhaustion burnout that reduced when wishful thinking coping was introduced as a predictor. Exploration of multiple mediator effects using bootstrap methods revealed that wishful thinking partially mediated the relationship between work demands and emotional exhaustion but practical coping did not. Practical coping had a main effect relationship with personal accomplishment, and there was evidence that support moderated the impact of work demands on personal accomplishment (although not fully consistent with theory). Study variables, other than personal accomplishment, were stable over 22 months but no longitudinal relationships between coping and burnout was found. These findings emphasise the importance of coping in managing work demands and for the development of burnout in support staff. (Contains 4 tables and 1 figure.)