Power loss is the most significant parameter in power system analysis and its adequate calculation directly effects the economic and technical evaluation. This paper aims to propose a multi-objective optimization algorithm which optimizes dc source magnitudes and switching angles to yield minimum THD in cascaded multilevel inverters. The optimization algorithm uses metaheuristic approach, namely Harmony Search algorithm. The effectiveness of the multi-objective algorithm has been tested with 11-level Cascaded H-Bridge Inverter with optimized DC voltage sources using MATLAB/Simulink. As the main objective of this research paper is to analyze total power loss, calculations of power loss are simplified using approximation of curves from datasheet values and experimental measurements. The simulation results, obtained using multi-objective optimization method, have been compared with basic SPWM, optimal minimization of THD, and it is confirmed that the multilevel inverter fired using multi- objective optimization technique has reduced power loss and minimum THD for a wide operating range of multilevel inverter.