Objective <p>Investigating the effects of sertraline on depressive symptoms and serum inflammatory factors in adolescents with depression to verify the relationship between depressive state and serum inflammatory factors.</p> Methods <p>Retrospective collection was conducted on 50 adolescent depression patients treated with sertraline admitted to a hospital from January 2021 to December 2022 as the observation group. By propensity score matching, 50 non pharmacological adolescent depression patients were matched as a control group in a 1:1 ratio. Kutcher Adolescent Depression Scale (KADS-11) scores were retrospectively analyzed before treatment (T1) and on 8th week after treatment (T5). At the same time, the scores of interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-11 (IL-11) scores, and interleukin-2 (IL-6), as well as tumor necrosis factor - α (TNF-α) before treatment (T1), on 1st week (T2), 2nd week (T3), 4th week (T4), and 8th week (T5) of the two groups were also retrospectively studied. Pearson correlation analysis was used to verify the relationship between depressive symptoms and serum inflammatory factors in adolescents with depression. Multiple linear regression analysis was used to find out the effect of serum inflammatory factors on depressive symptoms in adolescents with depression.</p> Results <p>Attention problems, body discomfort, and total score of KADS-11 in control group were significantly decreased compared with those before treatment at T5 (<i>P</i> &lt; 0.05). Every score and total scores of KADS-11 in observation group were significantly lower than those before treatment (<i>P</i> &lt; 0.05), and the data in observation group were lower than those in control group (<i>P</i> &lt; 0.05). According to repeated measurement ANOVA, there were statistically significant differences in IL-1β, IL-2, IL-6, and TNF-α levels between the two groups (<i>P</i> &lt; 0.05), and the change of serum inflammatory factors in the observation group was more obvious than that in the control group. Pearson correlation analysis showed that the total scores of KADS-11 were positively correlated with serum inflammatory factors (<i>r</i> = 0.881 ~ 0.932, <i>P</i> &lt; 0.05). Linear regression analysis showed that IL-1β, IL-2, IL-6, and TNF-α had positive effects on the total score of KADS-11 (B = 0.145–0.444, <i>P</i> &lt; 0.05).</p> Conclusion <p>Sertraline can effectively relieve the symptoms of depression in adolescents and reduce inflammation. Serum inflammatory factors have a significant relationship with depressive symptoms, so it can be considered as an evaluation index of treatment effect.</p>