Background <p>The process of conducting research has been shown to impact depression among undergraduate and graduate students in the sciences. While prior work has established that experiencing failure, negative social interactions, and insufficient guidance in research experiences can exacerbate students’ depressive symptoms, why these stressors in research worsen depressive symptoms has not been examined. Understanding the mechanisms underlying this relationship is integral to promoting mental health in science and consequently improving students’ learning and productivity. In this study, we aimed to assess whether Abramson’s Hopelessness Theory of Depression helps explain why encountering stressors in research can exacerbate science students’ depressive symptoms. We conducted semi-structured interviews with 74 researchers who identified as having depression: 24 undergraduate and 50 graduate students engaging in scientific research across 55 U.S. institutions. We used deductive coding to assess whether students made internal, stable, and global attributions when discussing why stressors in research exacerbated their depressive symptoms.</p> Results and conclusions <p>We found that the Hopelessness Theory of Depression helps explain why particular stressors in research can lead to worsening symptoms of depression among undergraduate and graduate researchers. Participants attributed stressors in research to internal, stable, and global causes, which engendered feelings of hopelessness, consequently exacerbating depressive symptoms. This work serves as a proof of concept for the Hopelessness Theory of Depression in the context of U.S. undergraduate and graduate scientific research experiences. The study provides insight into how interventions can target individuals’ thought processes to alleviate depressive symptoms in the context of research experiences to promote learning and productivity.</p>