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The COVID-19 pandemic adversely affected several aspects of daily life and seriously threatened public health. The main aim of this study was to investigate the differences in human response to SARS-CoV-2 virus infection depending on sex, based on emergency medical team (EMT) interventions. The study was conducted in north-eastern Poland and were based on 12,110 EMT interventions, in which SARS-CoV-2 virus infection was indicated as an ICD-10 codification-based diagnosis. The study used descriptive statistics, Mann-Whitney U, and Chi-square tests. Patients infected with SARS-CoV-2 accounted for 4.6% of all EMT interventions during the period under analysis. Younger males were more likely to acquire infection than females (p < 0.001)-the median (Me) age was 68.0 vs. 71.0. In infected males, a life-threatening condition was diagnosed more frequently than in females (p < 0.001; 53.6% vs. 48.6%). Females remained at the place of call more often (p < 0.001; 46.2% vs. 39.6%), whereas males were more frequently transported to hospital (p < 0.001; 59.3% vs. 53.3%) and were more likely to be declared dead (p = 0.002; 0.8% vs. 0.4%). In males, the predominant complaints included dyspnoea (p < 0.001; 47.2% vs. 38.4%), abnormalities of breathing (p = 0.001; 40.1% vs. 37.2%) and cyanosis (p < 0.001; 3.2% vs. 2.1%), whereas, in females, these included vomiting (p < 0.001; 9.4% vs. 4.4%), diarrhoea (p < 0.001; 7.8% vs. 5.0%) and collapse (p = 0.034; 8.6% vs. 7.5%). The blood oxygen saturation value (SpO₂) (p < 0.001) in males (Me = 92.0) was significantly lower than that in females (Me = 94.0). Oxygen therapy (p < 0.001; 29.0% vs. 24.0%) was more frequently associated with males. The course of the COVID-19 infection depends on the sex of the patient, and male sex is a risk factor for its severe course. Therefore, public health strategies and actions should take into account sex as an important factor in the disease process, prevention and the fight against the pandemic.