Peru suffered the highest mortality rates worldwide during the COVID-19 pandemic. In this study, we assessed the Peruvian districts' all causes of mortality-associated sociodemographic factors before and during the COVID-19 pandemic using mixed-effects Poisson regression models. During the pre-pandemic and the first four COVID-19 waves, the Peruvian districts reported mean weekly mortality of 22.3 (standard deviation 40.4), 29.2 (38.7), 32.5 (47.2), 26.8 (38.9), and 24.4 (38.0), respectively. We observed that before the COVID-19 pandemic, the districts' weekly deaths were associated with the human development index ((HDI) adjusted incidence rate ratio (aIRR) 0.11 (95% confidence interval 0.11–0.12)), accessibility (aIRR 0.99 (0.99–0.99)), poverty (aIRR 0.99 (0.99–0.99)), and anemia (aIRR 0.99 (0.99–0.99)). However, during each of the first four COVID-19 waves, the magnitude of association between the districts' weekly deaths and HDI decreased (first, aIRR 0.61 (0.58−0.64); second, aIRR 0.54 (0.52−0.57); third, aIRR 0.20 (0.19−0.22); fourth, aIRR 0.17 (0.15−0.19)), but the association with accessibility (aIRR 0.99 (0.99–0.99)), poverty (aIRR 0.99 (0.99–0.99)), and anemia (aIRR 0.99(0.99–0.99)) remain constant. Before and during the COVID-19 pandemic, a solid association existed between all-cause mortality and the district's sociodemographics, increasing with lower HDI, accessibility, poverty, and anemia rates.