The aim of this study was to explore in a hospital setting the relationships between work motivation and stress among psychologists working in hospitals. The second aim was to identify the respective roles of threat appraisal and challenge appraisal in this population. We expected work stress to have a motivational impact in the workplace, with primary cognitive appraisal (e.g., threat or challenge) playing a crucial role. The study included a large sample of 430 French psychologists recruited in French hospitals with a mean age of 33.68 ± 8.73 years. We assessed perceived work stress, work motivation, and primary cognitive appraisal. Analysis showed two main outcomes. First, perceived stress in the workplace impacts work motivation; specifically, the higher the perceived stress, the less motivation is self-determined. Second, threat cognitive appraisal has a direct and negative motivational impact, but also an indirect impact via perceived stress. However, appraisal of work as a cognitive challenge also directly and positively impacts motivation in the workplace, without indirect effects. Finally, work stress, work motivation and primary cognitive appraisals are significantly related with the workplace. These relationships support complementarity with the Transactional Model of Stress and SDT motivational approach in a theoretical and practical perspective in the workplace.