Particulate matter air pollution is a pervasive global risk factor implicated in the genesis of pulmonary and cardiovascular disease. Although the effects of prolonged exposure to air pollution are well characterized with respect to pulmonary and cardiovascular function, comparatively little is known about the impact of particulate matter on affective and cognitive processes. The central nervous system may be adversely affected by activation of reactive oxygen species and pro-inflammatory pathways that accompany particulate matter pollution. Thus, we investigated whether long-term exposure to ambient fine airborne particulate matter (<2.5 μm (PM(2.5))) affects cognition, affective responses, hippocampal inflammatory cytokines and neuronal morphology. Male mice were exposed to either PM(2.5) or filtered air (FA) for 10 months. PM(2.5) mice displayed more depressive-like responses and impairments in spatial learning and memory as compared with mice exposed to FA. Hippocampal pro-inflammatory cytokine expression was elevated among PM(2.5) mice. Apical dendritic spine density and dendritic branching were decreased in the hippocampal CA1 and CA3 regions, respectively, of PM(2.5) mice. Taken together, these data suggest that long-term exposure to particulate air pollution levels typical of exposure in major cities around the globe can alter affective responses and impair cognition.