Abstract: Exposure to outdoor air pollution has been shown to increase asthma symptoms. We assessed the potential role of particulate matter with aerodynamic diameter <2.5 μm (PM2.5) on respiratory condition in schoolchildren in the south Mediterranean area. A total of 2400 children aged 11–14 years were recruited, and data on their symptoms were collected through an ISAAC (International Study of Asthma and Allergies in Childhood)-based questionnaire. Outdoor PM2.5 was collected for 48 consecutive hours in the schoolyards of their schools and selected residential outdoor areas. The levels of PM2.5 were measured, along with its elemental composition. The incidence of an acute respiratory illness within the first 2 years of life was higher amongst Sicilian children when compared to Maltese children (29.7% vs. 13.5% respectively, p < 0.0001). Malta had a significantly higher prevalence of doctor‐diagnosed asthma, when compared to Sicily (18.0% Malta vs. 7.5% Sicily, p <0.0001). Similarly, current asthma (7.8% vs. 2.9%, p < 0.0001) and use of asthma medication in the last 12 months (12.1% vs. 4.9%, p < 0.0001) were more frequent amongst Maltese children. Total median PM2.5 was 12.9 μg/m3 in Sicily and 17.9 μg/m3 in Malta. PM2.5 levels were highest in the Maltese urban town of Hamrun (23.6 μg/m3), while lowest in the rural Sicilian town of Niscemi (10.9 μg/m3, p < 0.0001). Hamrun also exhibited the highest levels of nickel, vanadium, lead, zinc, antimony, and manganese, whilst the Sicilian city of Gela had the highest levels of cadmium, and the highest level of PM2.5 when compared to rural Sicily. Elevated levels of PM2.5 were positively associated with the prevalence of doctor diagnosed asthma (odds ratio (OR) 1.05), current asthma (OR 1.06), and use of asthma medication (OR 1.06). All elements in PM2.5 showed increased OR for doctor diagnosed asthma, while higher concentrations of Cd and Mn were associated with higher prevalence of rhinitis.