This work utilizes in situ transmission electron microscopy-based nanopillar compression to investigate the effect of electrochemical cycling on the mechanical properties of LiCoO2. The ultimate strength of LiCoO2 in the pristine state, and after 1 and 11 cycles are 5.62 +/- 0.22 GPa, 3.91 +/- 1.22 GPa, and 2.27 +/- 1.07 GPa, respectively. The reduced average yield strengths and the large standard deviations of cycled samples, relative to the pristine powder, are hypothesized to result from nonuniform accumulation of Li+ site-point defects during cycling; either H+ or Li+ vacancies. Density functional theory calculations support our hypothesized link between a nonuniform Li site-point defect distribution in the cathode and reduction in the materials cohesive strength.