Background: The COVID-19 pandemic had negatively impact mental health worldwide. High prevalence of stress had been previously reported in populations during this context. Many theoretical frameworks had been proposed for explaining the stress process, we aim to proposed and explanatory model for the genesis of perceived stress in Peruvian general population. Method: We conducted an online survey in Peruvian general population assessing sociodemographic variables and evaluating mental health conditions by using The Perceived Stress Scale (PSS-10), Positive Affect and Negative Affect Scale (PANAS), Generalized Anxiety Disorder scale (GAD-7), Patient Health Questionnaire (PHQ-9), and a numerical rating scale (NRS) for fear of COVID-19. Correlation analysis was conducted for the variables of interest. Two regression models were constructed to explore related factor to the dimensions of perceived stress. Finally, a structural regression model was performed with the independent variables. Results: Data of 210 individuals was analyzed. Ages ranged from 15 to 74 years and 39% were women. Additionally, 65.2% of the participants had at least one mental health conditions (depression, anxiety, or stress symptoms). Perceived self-efficacy and positive affect (PA) were correlated, as perceived helplessness with anxious symptoms and negative affect (NA). Regression analysis showed that sex, anxiety symptoms, and NA explained perceived helplessness while positive and NA explained self-efficacy. The structural regression model analysis identified that fear of COVID-19 (composed of fear of infecting others and fear of contagion), predicted mental health conditions (i.e., depressive or anxiety symptoms); also, mental health conditions were predicted by PA and NA. Perceived helplessness and Perceived self-efficacy were interrelated and represented the perceived stress variable. Conclusion: We proposed an explanatory model of perceived stress based on two correlated dimensions (self-efficacy and helplessness) in the Peruvian general population during the context of the COVID-19 pandemic, with two out of three individuals surveyed having at least one mental health condition.