Background The ongoing COVID-19 pandemic has revealed gender-specific differences between general practitioners in adapting to the posed challenges. As primary care workforce is becoming increasingly female, in many countries, it is essential to take a closer look at gender-specific influences when the global health care system is confronted with a crisis. Objective To explore gender-specific differences in the perceived working conditions and gender-specific differences in challenges facing GPs at the beginning of the COVID-19 pandemic in 2020. Design Online survey in seven countries. Participants 2,602 GPs from seven countries (Austria, Australia, Switzerland, Germany, Hungary, Italy, Slovenia). Of the respondents, 44.4% (n = 1,155) were women. Main Measures Online survey. We focused on gender-specific differences in general practitioners’ perceptions of working conditions at the beginning of the COVID-19 pandemic in 2020. Key Results Female GPs rated their skills and self-confidence significantly lower than male GPs (f: 7.1, 95%CI: 6.9–7.3 vs. m: 7.6, 95%CI 7.4–7.8; p < .001), and their perceived risk (concerned about becoming infected or infecting others) higher than men (f: 5.7, 95%CI: 5.4–6.0 vs. m: 5.1, 95%CI: 4.8–5.5; p = .011). Among female GPs, low self-confidence in the treatment of COVID-19 patients appear to be common. Results were similar in all of the participating countries. Conclusions Female and male GPs differed in terms of their self-confidence when dealing with COVID-19-related issues and their perceptions of the risks arising from the pandemic. To ensure optimal medical care, it is important that GPs realistically assess their own abilities and overall risk.