COVID-19 causes physical and psychological stressors. The aim of this study is to analyze the relationship of depression, anxiety, stress levels (DASS-21), salivary cortisol, and platelet-lymphocyte ratio (PLR) with severity in COVID-19 patients. Methods: This is a cohort prospective study. Inclusion criteria were new patient at isolation room of Dr. Soetomo Hospital Surabaya with a confirmed COVID-19, 21-60 years, could answer a questionnaire. Measurements of DASS-21, salivary cortisol levels

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... at 7-9 a.m), PLR, and severity were carried out on day-0, 3, and 6 during hospitalization. Bivariate and multivariate (logistic regression) analyses were conducted to assess the relationship between variables. Results: 46 subjects were included in this study. On day-0, there were 34.8% subjects with very severe levels of anxiety. DASS-21 score and PLR decreased significantly on day-3 and 6. The anxiety (p=0.002), lymphocyte (p=0.000), PLR (p=0.000), and salivary cortisol levels (p=0.032) were significantly different between the mild-moderate and severe group on day-0. In severe group, lymphocyte and salivary cortisol levels were lower than the mild-moderate group. On day-3, depression (p=0.021), anxiety (p=0.001), lymphocyte (p=0.025), and PLR (p=0.005) were significantly different between mild-moderate and severe group. In multivariate analysis, PLR on days 0 and 3 (respectively OR=1.015, p=0.012 and OR=1.010, p=0.013) and anxiety level on day-3 (OR=1.225, p=0.019) had a significant effect on the severity of COVID-19. Conclusion: Salivary cortisol was lower in the severe group on day 0. PLR on day-0 and 3 and anxiety level on day 3 were independent factors related to the severe case. Improvements in all variables were followed by decreasing COVID-19 severity.