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Aim To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. Methodology This is a prospective case–control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators was examined longitudinally in all subjects during six visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analysed by linear regression analyses and linear mixed‐model analyses. Results A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, granulocyte colony‐stimulating factor (p < .001), interleukin (IL)‐1β (p = .03) and IL‐4 (p = .01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e. 3 months after the tooth extraction, showed a significant reduction in IL‐10 (p = .03) and IL‐12p70 (p = .01). Conclusions The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low‐grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis.