<p>Air quality significantly impacts public health, contributing to respiratory and cardiovascular diseases. This study investigated the influence of the Great Sebkha of Oran (GSO) on PM2.5 concentrations and the role of meteorological factors in their variations. MODIS Terra and Aqua satellite data were used to analyze Aerosol Optical Depth (AOD 47), whereas van Donkelaar’s algorithm was used to estimate the PM2.5 levels. The results highlight significant spatiotemporal variations (2012–2023), with the highest concentrations recorded in 2018 (25.90 µg/m³) and the lowest in 2013 (17.46 µg/m³). Spatial analysis revealed persistently high PM2.5 levels (&gt; 35.5 µg/m³) in the southern and southeastern regions, which coincided with the GSO, with isolated hotspots near industrial zones and the port. Temporally, PM2.5 concentrations peak during dry, windy periods. Strong positive correlations were found between PM2.5 and temperature (R = 0.8476) and wind speed (R = 0.7099), while negative correlations were observed with soil moisture (R = -0.8210) and precipitation (R = -0.4933). Despite reduced anthropogenic activity during the COVID-19 pandemic, PM2.5 levels remained high, underscoring the significant contribution of the GSO. The study advocates for enhanced air quality monitoring, urban greening, and stricter regulations to mitigate PM2.5 emissions from natural and anthropogenic sources, ultimately improving public health.</p>