AbstractEndodontic freshly mixed sealers display toxic effects; however, these are significantly reduced and most become relatively inert in the set state but there is no information about the possible inflammatory reaction promoted by them. Four contemporary and different formulated endodontic set sealers (MTA Fillapex, BioRoot RCS, AH Plus, and Pulp Canal Sealer) were evaluated. Human periodontal ligament cells and human peripheral blood mononuclear cells were stimulated for 3, 6, 12 and 24 h. Interleukin‐6, tumour necrosis factor‐alpha, interleukin‐8 and interleukin‐10 concentrations were measured by enzyme‐linked immunosorbent assay. All endodontic set sealer eluates promoted a similar production (P ˃ 0.05) of the four cytokines. However, their concentrations decreased within a short time period to nearly undetectable concentrations after 24 h, suggesting that the studied endodontic set sealers do not possess inflammatory properties which has favoured their long‐term use in clinical practice.