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Lipids play an important role in coordinating and regulating metabolic and inflammatoryprocesses. Sprint interval training (SIT) is widely used to improve sports performance and healthoutcomes, but the current understanding of SIT-induced lipid metabolism and the correspondingsystemic inflammatory status modification remains controversial and limited, especially in maleadolescents. To answer these questions, twelve untrained male adolescents were recruited andunderwent 6 weeks of SIT. The pre- and post-training testing included analyses of peak oxygenconsumption (VO2peak), biometric data (weight and body composition), serum biochemical pa-rameters (fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-densitylipoprotein cholesterol, triacylglycerol, testosterone, and cortisol), inflammatory markers, and tar-geted lipidomics. After the 6-week SIT, the serum C-reactive protein (CRP), interleukin (IL)-1β, IL-2,IL-4, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β significantlydecreased (p < 0.05), whereas IL-6 and IL-10/TNF-α significantly increased (p < 0.05). In addition,the targeted lipidomics revealed changes in 296 lipids, of which 33 changed significantly (p < 0.05,fold change > 1.2 or <1/1.2). The correlation analysis revealed that the changes in the inflammatorymarkers were closely correlated with the changes in some of the lipids, such as LPC, HexCer, andFFA. In conclusion, the 6-week SIT induced significant changes in the inflammatory markers andcirculating lipid composition, offering health benefits to the population.