Working memory is an important mental capacity that is compromised following sleep deprivation (SD). To understand how working memory load interacts with state to influence brain activation in load-sensitive regions, and the extent to which SD-related changes are common across different loads, we used fMRI to study twelve healthy subjects following 24 h of SD using a verbal n-back task with three load levels. Performance decline was observed by way of reduced accuracy and slower response times following SD. The left prefrontal region and thalamus showed load dependent activity modulation that interacted with state. The right parietal and anterior medial frontal regions showed load dependent changes in activity as well as an effect of state. The anterior cingulate and occipital regions showed activation that displayed state effects that were independent of working memory load. These findings represent a step toward identifying how different brain regions exhibit varying vulnerability to the deleterious effects of SD on working memory.