Seasonal allergy is associated with increased prevalence of psychiatric symptoms and disorders, as well as fatigue and cognitive difficulties that aggravate during pollen season. It is unclear if this results from the impact of peripheral allergic inflammation on the immune system in brain. We studied 15 allergic patients and 13 healthy controls in and out of pollen season in a balanced design. Positron emission tomography (PET) and the radioligand [11C]PBR28 was used to measure TSPO (translocator protein); a marker for immune cells (including microglia) in the brain. TSPO binding was quantified as total distribution volume of [11C]PBR28 in grey matter, controlled for polymorphisms in the TSPO gene that affect binding affinity. There were no differences between allergics and controls in TSPO levels, and no interaction with time of year. In peripheral blood, there was an increase in TNF-alpha (p = 0.04) but not IL-6 in allergics during pollen season. IL-5 was higher in allergics, and increased further during pollen season, with a corresponding pattern in the ratio between Th2 and Th1 cytokines (IL-5/IFN gamma; p’s