Exposure to air pollution has been shown to increase the risk of developing chronic respiratory diseases. The largest crude oil first treatment plant in Italy emits harmful polluting substances. This cross-sectional study assesses the occurrence of respiratory symptoms in a sample of the adult population living near the plant. A proximal and a reference area were defined in order to recruit 200 subjects. Each subject performed a spirometry test and completed a questionnaire. Associations between the distance from the plant and selected respiratory outcomes were assessed (distance-based approach). The prevalence of outcomes between a proximal and a reference area (area-based approach) were also compared. Odds ratios were adjusted for potential confounders. Living near the plant was associated with a higher prevalence of respiratory symptoms, with significant associations for severe dyspnoea equivalent to the halving of risk as the distance of residence from the plant increased by 1 km (adjusted odds ratio (OR) 0.48, confidence interval at the 95% probability level (95% CI): 0.25–0.92). Several signals emerged for respiratory allergic symptoms. The area-based approach generally confirmed the results obtained with the distance-based approach. This is the first study to be carried out on a crude oil first treatment plant aimed at assessing the association with the occurrence of respiratory symptoms. These findings contribute to the evidence supporting the need for a space–time surveillance system in the investigated area.