A systematic review and meta-analysis of 21 studies with 359 healthy participants evaluated the acute effects of a single session of sprint interval training (SIT) on the immune system. A single session of SIT significantly increased total leukocyte (SMD = 2.68, 95% CI: 1.79–3.57), neutrophil (SMD = 1.04, 95% CI: 0.75–1.34) and lymphocyte (SMD = 3.83, 95% CI: 1.07–6.59) counts, with lymphocyte counts showing a U-shaped relationship with repeat length. Interleukin-6 (IL-6) was significantly increased (SMD = 1.10, 95% CI: 0.49–1.71), with a twofold stronger response in trained athletes compared to untrained. Salivary IgA (sIgA) remained stable in the trained (SMD = 0.07, 95% CI: -0.31–0.45) but was variable in the untrained. IL-10 plasma concentration showed a small non-significant increase (SMD = 0.18, 95% CI: -0.06–0.43). Athletes showed a different immunometabolic profile with higher IL-6 and stable mucosal immunity, while untrained had more variable responses.