Metabolomics represents a powerful tool for measuring environmental exposures and biological responses to unveil potential mechanisms. Few studies have investigated the effects of exposure to fine particulate matter (PM) longitudinally on serum metabolomics in regions with high-level PM. Therefore, we examined the changes of serum metabolomics corresponding to individual PM exposure levels in spring and autumn among 63 healthy college students in Baoding city, Hebei, China. The metabolic profiling was determined by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The average level of individual PM in the spring was 1.82-fold higher than in the autumn (240 μg/m vs 132 μg/m). Males were exposed to a higher level of PM than females in the spring. Metabolic profiling was clearly separated by orthogonal partial least square-discriminant analysis in males but not in females. In the analysis of the associations between the metabolome and PM of the two seasons, the changes of 14 serum metabolites were significantly associated with PM in males. The metabolites related to heme metabolism (bilirubin, biliverdin), energy metabolism and oxidative stress (2-Octenoylcarnitine, N-Heptanoylglycine, and acetylcysteine), phospholipid metabolism (lysophosphatidic acid, phospholipid acid, and lysophosphatidylethanolamine), and tryptophan metabolism (N-Acetylserotonin, indolepyruvate, and melatonin) were decreased in the range of 2.16%-6.80% for each 10 μg/m increase of PM, while thyrotropin-releasing hormone, glutathione, and phosphatidylethanolamine related to energy metabolism and oxidative stress, and phospholipid metabolism were increased in the range of 2.95%-4.90% for each 10 μg/m increase of PM. This longitudinal study suggests that higher PM exposure may induce perturbations in serum metabolic signaling related to oxidative stress and inflammation, and males may be more prone to these metabolic perturbations.