This paper investigates the predicting role of resilience and meaning in life on perceived stress of frontline health care workers treating patients with COVID-19. To measure the variables, a set of online questionnaires including Perceived Stress Questionnaire (PSS), Meaning of Life Questionnaire (MLQ), and Resilience Questionnaire (CD_RISC) was prepared. Presence of meaning, search for meaning, notion of personal competence, tolerance and trust in intuition, acceptance and secure relationships, control, and spiritual influences were examined as predictors of perceived stress. Several frontline health care workers were included in the final study. To analyze the data, regression analysis method was used with SPSS-20 software. The results showed that: 1) the regression model of resilience and the presence of meaning in the life of health care workers on their perceived stress was significant (F (6,229)=45.14, p<0.0001); 2) the predictive variables, in total, could explain 53% of the variance of perceived stress; 3) perceived stress correlated negatively with presence of meaning (β = −0.380, p<0.05), with acceptance and secure relationships (β = −0.620, p< 0.05), with control (β = −0.609, p<0.05), and positively correlated with spiritual influences (β = 0.465, p<0.05). Finding and maintaining meaning in life and improving acceptance, secure relationships, and sense of control would reduce perceived stress of frontline health care workers.