Introduction Endodontic-periodontal (EP) lesions require both endodontic and periodontal therapies. Impermeable sealing of the root canal system after cleaning and shaping is essential for a successful endodontic treatment. However, complete healing of the hard and soft tissue lesions takes time, and diseased bone, periodontal ligament, and tooth fibrous joints are reported to have an increased failure risk for a given load. Considering that EP lesions may affect the biomechanics of teeth, this finite elemental analysis study aimed to test the effect of root fillings on stress distribution in premolars with EP lesions. Methods Three finite elemental analysis models representing 3 different types of EP lesions (primary endodontic disease [PED], PED with secondary periodontic involvement, and true combined) were created. The root canals were assumed as nonfilled or filled with gutta-percha, gutta-percha/apical mineral trioxide aggregate (MTA) plug, and MTA-based sealer. Materials used were assumed to be homogenous and isotropic. A 300-N load was applied from the buccal cusp of the crown with a 135° angle. The Cosmoworks structural-analysis program (SolidWorks Corp, Waltham, MA) was used for analysis. Results were presented considering von Mises criteria. Results Stresses at the root apex increased with an increase in lesion dimensions. Root filling did not affect stress distribution in the PED model. An MTA plug or MTA-based sealer created more stress areas within the root compared with the others in the models representing PED with periodontic involvement and true combined lesions. Conclusions Stresses at the apical end of the root increase with increases in lesion dimensions. MTA-based sealers or an MTA plug creates more stresses when there is periodontic involvement or a true combined lesion.