Video-conferencing use has increased significantly in recent years, highlighting the need to understand its impact on individuals' psychological experiences. We conducted two large survey studies (total N = 3920) to examine the relationship between video-conferencing, video-conference fatigue (Zoom fatigue), and individuals' feelings of social connection, social skills, and life satisfaction. Study 1 showed that people tended to feel more connected to others when video-conference meetings were frequent, brief and conducted with small groups, compared to long meetings with many participants. As meetings became longer and more frequent, people felt less socially connected and reported increased video-conference fatigue. Feeling cognitively or emotionally exhausted from engaging in video-conferencing may limit the ability to meaningfully engage with others in the call. In Study 2, mediation analyses indicated that increased video-conferencing could undermine life satisfaction by increasing video-conference fatigue. Furthermore, we compared participants’ perceptions of their social skills between in-person and video-conferencing meetings, and found people consistently felt less skilled in video-conferences than during in-person meetings. We discuss these findings in the context of widespread remote work and the need to protect well-being in this digital era. •Frequent, interactive, small-group brief video-conference meetings increased how connected people felt to others.•As Meetings became longer and more frequent, people became less socially connected because they developed Zoom fatigue.•In terms of social skills, people felt less skilled in video-conferences than during in-person meetings.•Video-conferencing had adverse effects on well-being because of Zoom fatigue.