We evaluated the effect of three monthly intravitreal injections of aflibercept on the serum concentration of interleukin 17A (IL-17A), monocyte chemoattractant protein 1 (MCP-1/CCL2), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in treatment-naive patients with neovascular age-related macular degeneration (nAMD). Twenty-two eyes of twenty-two patients with nAMD scheduled for the initial loading phase of intravitreal aflibercept (2 mg/0.05 mL) were included. Serum VEGF, PlGF, MCP-1/CCL2 and IL-17A levels were determined four times in each individual—just before the first injection, 2–3 days after the first injection, just before the third injection, and then 2–3 days after the third aflibercept injection. A statistically significant difference was found between the serum PlGF and IL-17A levels measured before the first injection and after the initial loading phase, with a mean value (MV) of 440.884 vs. 302.151 (p = 0.023) for PlGF and MV = 139.088 pg/mL vs. 151.233 pg/mL (p = 0.016) for IL-17A, respectively. There were no statistically significant differences for VEGF and MCP-1/CCL2 between any of the compared measurements. We reveal that repeated injections of aflibercept promote an increase in serum IL-17A concentration, which may lead to a systemic inflammatory response mediated by IL-17A, but not by MCP-1.