As a consequence of lockdowns due to the coronavirus disease (COVID-19) and the resulting restricted social mobility, several billion people worldwide have recently had to replace physical face-to-face communication with computer-mediated interaction. Notably, the adoption rates of videoconferencing increased significantly in 2020, predominantly because videoconferencing resembles face-to-face interaction. Tools such as Zoom, Microsoft Teams, and Cisco Webex are used by hundreds of millions of people today. Videoconferencing may bring benefits (e.g., saving of travel costs, preservation of environment). However, prolonged and inappropriate use of videoconferencing may also have an enormous stress potential. A new phenomenon and term emerged, Zoom fatigue, a synonym for videoconference fatigue. This paper develops a definition for Zoom fatigue and presents a conceptual framework that explores the major root causes of videoconferencing fatigue and stress. The development of the framework draws upon media naturalness theory and its underlying theorizing is based on research published across various scientific fields, including the disciplines of both behavioral science and neuroscience. Based on this theoretical foundation, hypotheses are outlined. Moreover, implications for research and practice are discussed.