Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan–Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971–12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048–2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208–9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187–2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279–3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523–86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049–2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092–3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780–6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240–2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality.