Background Cardiovascular disease (CVD) is the main cause of death in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN). This study aimed to evaluate the prevalence of myocardial injury among patients with SLE without nephritis and patients with LN, determine whether serum high-sensitivity cardiac troponin T and creatine phosphokinase-MB (CKMB) might help to identify patients with LN at risk for CVD, and identify LN as a risk factor for myocardial injury. Patients and methods This study was conducted on 50 patients (30 patients with LN and 20 patients with SLE without nephritis). The SLE disease activity index (SLEDAI) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC/DI) were assessed. Laboratory investigations, cardiac enzymes (Hs-TnT and CKMB), and transthoracic echocardiography were performed. Results The results demonstrated a higher prevalence of CVD in patients with LN. A total of 28 patients with LN (93.3%) vs 10 patients with SLE (50%) had detectable high-sensitivity troponin (Hs-TnT) levels, with a mean 29.77±18.22 vs 7.2±6.21 ng/l, respectively. The mean value of CKMB was higher in patients with LN than patients with SLE (23.9±18.6 vs 14.8±9.4 μg/l, respectively). Multilinear regression analysis for Hs-TnT revealed that low estimated glomerular filtration rate, high urinary albumin-to-creatinine ratio, low ejection fraction, and different ECHO diameters were the most statistically significant predictors of troponin elevation, with a P value less than 0.05. The strongest renal predictors of CKMB were estimated glomerular filtration rate and proteinuria, with a P value less than 0.05. Conclusion CVD is more in patients with LN than patients with SLE. Hs-TnT levels is a signature of subclinical cardiac disease, which could be used to identify at-risk individuals. CKMB and echocardiography lack adequate sensitivity for the diagnosis of myocardial injury in patients with LN.