The detrimental influence of air pollution on mortality has been established in a series of studies. The majority of them were conducted in large, highly polluted cities—there is a lack of studies from small, relatively clean regions. The aim was to analyze the short-term impact of particulate matters (PMs) on mortality in north-eastern Poland. Time-stratified case-crossover design was performed for mortality in years 2008–2017. Daily concentrations of PM2.5 (28.4 µg/m3, interquartile range (IQR) = 25.2) vs. (12.6 µg/m3, IQR = 9.0) and PM10 (29.0 µg/m3, IQR = 18.0) vs. (21.7 µg/m3, IQR = 14.5) were higher in Łomża than Suwałki (p < 0.001). Impact of PM2.5 on mortality was recorded in Łomża (odds ratio (OR) for IQR increase 1.061, 1.017–1.105, p = 0.06, lag 0) and Suwałki (OR for IQR increase 1.044, 1.001–1.089, p = 0.004, lag 0). PM10 had an impact on mortality in Łomża (OR for IQR increase 1.028, 1.000–1.058, p = 0.049, lag 1). Cardiovascular mortality was affected by increase of PM2.5 in Łomża (1.086, 1.020–1.156, p = 0.01) and Suwałki (1.085, 1.005–1.171, p = 0.04). PM2.5 had an influence on respiratory mortality in Łomża (1.163, 1.021–1.380, p = 0.03, lag 1). In the whole studied region, despite differences in the air quality, the influence of PMs on mortality was observed.