Introduction The COVID-19 pandemic has initiated an upheaval in society and has been the cause of considerable stress during this period. Healthcare professionals have been on the front line during this health crisis, particularly paramedical staff. The aim of this study was to assess the high level of stress of healthcare workers during the first wave of the pandemic. Materials and methods The COVISTRESS international study is a questionnaire disseminated online collecting demographic and stress-related data over the globe, during the pandemic. Stress levels were evaluated using non-calibrated visual analog scale, from 0 (no stress) to 100 (maximal stress). Results Among the 13,537 individuals from 44 countries who completed the survey from January to June 2020, we included 10,051 workers (including 1379 healthcare workers, 631 medical doctors and 748 paramedical staff). The stress levels during the first wave of the pandemic were 57.8 ± 33 in the whole cohort, 65.3 ± 29.1 in medical doctors, and 73.6 ± 27.7 in paramedical staff. Healthcare professionals and especially paramedical staff had the highest levels of stress (p < 0.001 vs non-healthcare workers). Across all occupational categories, women had systematically significantly higher levels of work-related stress than men (p < 0.001). There was a negative correlation between age and stress level (r = -0.098, p < 0.001). Healthcare professionals demonstrated an increased risk of very-high stress levels (>80) compared to other workers (OR = 2.13, 95% CI 1.87–2.41). Paramedical staff risk for very-high levels of stress was higher than doctors’ (1.88, 1.50–2.34). The risk of high levels of stress also increased in women (1.83, 1.61–2.09; p < 0.001 vs. men) and in people aged <50 (1.45, 1.26–1.66; p < 0.001 vs. aged >50). Conclusions The first wave of the pandemic was a major stressful event for healthcare workers, especially paramedical staff. Among individuals, women were the most at risk while age was a protective factor.