As the central strain dimension of burnout, emotional exhaustion is a popular indicator of poor mental health in work and organizational psychology. Based on the job demands-resources (JD-R) model, the present article focuses on antecedents of and processes leading to emotional exhaustion. We hypothesized that sickness presenteeism (conceptualized as active and problem-focused coping) would partially mediate the relationship between work characteristics (workload and coworker support) and emotional exhaustion. Additionally, we examined a potential interaction between workload and coworker support, hypothesizing that a combination of high workload and low coworker support would produce the highest levels of sickness presenteeism. Participants were 462 employees working in a research funding organization in Germany who were given a validated multi-item measure to assess sickness presenteeism. The results of structural equation modeling strongly supported most hypotheses: The effects of coworker support and workload on emotional exhaustion were fully or at least partially mediated by sickness presenteeism. However, hierarchical regression analyses did not support the proposed interaction effect. It is concluded that sickness presenteeism may help to deliver a better understanding of the effects of the working environment on emotional exhaustion. Implications for the JD-R model and for workplace health promotion are discussed.