Background: Apical periodontitis (AP) is an inflammatory disorder of the periapical tissues caused by the persistence of a microbial infection within the root canal system of the affected tooth. Clinically, it is symptomatic or asymptomatic depending on several factors such as the type of microorganisms, bacterial load, immunological reaction, and local tissue mediators. Chronic or asymptomatic infections may initiate and modulate intravascular accumulation of inflammatory cells resulting in endothelial dysfunction which subsequently represents a possible systemic inflammatory burden. Aim: The present study aimed to evaluate the relationship between asymptomatic AP and systemic inflammatory burden by assessing the levels of chronic inflammatory cells. Methodology: A total of 25 patients diagnosed with asymptomatic AP who showed a negative response to the pulp sensitivity test with no history of any systemic diseases were included in this preliminary prospective observational study. Blood samples were collected at each phase of the study, and a complete hemogram was carried out. All hematological parameters were recorded before and after root canal therapy and they were analyzed for statistical significance at p <.05 using IBMSPSSStatistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). Results: Evaluation of the mean total leukocyte count (TLC), lymphocyte, and eosinophil cell count showed a significant reduction in the number of cells before and after root canal therapy treatment respectively (p<.05). One-way analysis of variance also revealed statistical significance at p < .05 with a weak positive correlation between the TLC, lymphocyte, and eosinophil count before and after treatment. Conclusion: The present study showed that systemically healthy individuals with asymptomatic AP had increased inflammatory burden in the circulation, and thus, it is essential to identify and quantify the risk associated. It was evident that complete healing of the asymptomatic AP lesions results in an overall reduction of systemic inflammatory cells ultimately reducing the burden and risk of associated systemic inflammatory diseases.