Purpose <p>To determine whether serum semaphorin 3&#xa0;A (Sema3A) and interleukin 6 (IL-6) play a role in the common etiopathogenesis of nAMD and nAMD-associated systemic diseases by evaluating these mediators levels.</p> Methods <p>This prospective case–control study included 74 patients divided into nAMD (<i>n</i> = 33) and a control group (<i>n</i> = 41). Serum Sema3A and IL-6 levels were analyzed using the enzyme-linked immunosorbent assay.</p> Results <p>The nAMD group had a statistically higher IL-6 level [5,9 (1–16,9) pg/mL], compared to the control group [1,5 (0,38 − 2,96) pg/mL] (<i>p</i> &lt; 0.001). On the other hand, the Sema3A level of the nAMD group was lower at [26,3 (11,5-100) ng/mL] compared to the control group at [44,7 (16,8-100) ng/mL] (<i>p</i> &lt; 0.001). The IL-6 level in the hypertension (+) group [2,5 (0,5–16,9) pg/ml] was significantly higher than that in the hypertension (-) group [1,7 (0,4–15,3) pg/ml] (<i>p</i> &lt; 0.001). No significant difference was found between the hypertension (+) and hypertension (−) groups in terms of SEMA3A level. There was a negative correlation between serum SEMA3A and serum IL-6 levels of the whole participants (<i>p</i> &lt; 0.001, <i>r</i>=-0.471).</p> Conclusions <p>Decreased levels of the anti-inflammatory and anti-angiogenic mediator Sema3A and increased levels of inflammatory mediator IL-6 detected in nAMD suggest that these molecules may play a role in systemic manifestations of this syndrome, such as inflammation, cardiovascular diseases, atrial fibrillation, and Alzheimer’s disease.</p> Clinical trial number <p>Not applicable.</p>