Fine particulate matter that have a diameter of <2.5 μm (PM2.5) are an important factor of anthropogenic pollution since they are associated with the development of acute respiratory illnesses. The aim of this prospective study is to examine the correlation between PM2.5 levels in the semi-urban city of Volos and Emergency Department (ED) visits for respiratory causes. ED visits from patients with asthma, pneumonia and upper respiratory infection (URI) were recorded during a one-year period. The 24 h PM2.5 pollution data were collected in a prospective manner by using twelve fully automated air quality monitoring stations. PM2.5 levels exceeded the daily limit during 48.6% of the study period, with the mean PM2.5 concentration being 30.03 ± 17.47 μg/m3. PM2.5 levels were significantly higher during winter. When PM2.5 levels were beyond the daily limit, there was a statistically significant increase in respiratory-related ED visits (1.77 vs. 2.22 visits per day; p: 0.018). PM2.5 levels were also statistically significantly related to the number of URI-related ED visits (0.71 vs. 0.99 visits/day; p = 0.01). The temperature was negatively correlated with ED visits (r: −0.21; p < 0.001) and age was found to be positively correlated with ED visits (r: 0.69; p < 0.001), while no statistically significant correlation was found concerning humidity (r: 0.03; p = 0.58). In conclusion, PM2.5 levels had a significant effect on ED visits for respiratory causes in the city of Volos.