Environmental hazards and/or pandemics may push humans to use different protective methods to maintain their well-being. This study aimed to identify populations vulnerable to psychometric challenges and fatigue during the Coronavirus Disease (COVID-19) pandemic in Kazakhstan. A total of 1,592 participants were recruited and asked to complete the Multidimensional Fatigue Inventory-20 (MFI-20). Participants were classified according to gender and age. Data were analyzed using the Chi-square test (x2) and MedCalc to detect the odds of MFI-scales with a score ≥12 in women compared to men. Young women had significantly higher odds (OR) of reduced activity (OR 2.4, p<0.0001), physical (OR 2.5, p<0.0001), and mental fatigue (OR 3.4, p<0.0001) than young men. Middle-aged women had significantly higher odds of general fatigue (OR 2.1; p<0.0001), reduced motivation (OR 2.1, p<0.0001), physical (OR 2.1, p<0.0001), and mental fatigue (OR 1.9, p<0.0001) than did middle-aged men. Elderly women had significantly higher odds of general fatigue (OR 3.6, p<0.0001), reduced motivation (OR 3.5, p<0.0001), and physical fatigue (OR 3.5, p<0.0001) than men in the same age category. The study highlights that women were more susceptible, with significantly increased odds of experiencing various aspects of fatigue syndrome compared to men during the COVID-19 pandemic in Kazakhstan. Therefore, it is necessary to investigate individual behavioral changes to help identify vulnerable populations and provide relevant evidence for developing protocols and guidelines during pandemics and/or outbreaks.