Background: Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Methods: Fifty-six rats were exposed either to CIH (nadir O₂ 4-5%) or sham (handled normoxic controls, HC), 8 hours per day for 6 weeks. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Results: Compared to HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH: 141.3±33.1 vs. HC 184.4±21.2 ml/min/kg, p<0.01), LV maximal positive dP/dt, and maximal negative dP/dt. CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3564±354 vs. HC 2628±242 µm², p<0.05) and cell length (CIH 148±23 vs. HC 115±16 µm, p<0.05), elevated TUNEL-stained positive cell number (CIH 98±45 vs. HC 15±13, p<0.01), elevated caspase-3 activity (906±249 vs. 2275±1169 pmol/min/mg, p<0.05), and elevated expression of several remodeling gene markers including c-fos, atrial natriuretic peptide, -myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, nor in LV collagen deposition on trichrome-stained slices. Conclusion: CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level.