Subsequently, the early reactivation or old human cytomegalovirus (HCMV) infection may be interfere with IgE and interleukin-33 (IL-33) levels disturbances throughout the life intervals and act as synergistic factors to play a significant role in the pathogenesis of various diseases; like asthma or coronary heart diseases (CHD). The main subject of the current study was to determine the role of CMV infection onto IgE levels and IL-33 disturbances in the pathogenesis of asthma and atherosclerosis as a case-control study. A total of 175 participants were with a mean age of 38.17 ± 7.51 years [age range: 26–52] years, which were distributed as patients with atherosclerosis (n=50) and asthmatic patients (n=50) as the cases of our study and 75 healthy subjects as a control group. Both groups of asthmatic and atherosclerosis patients show a significant association with the seropositivity of CMV-IgG which was detected in 33 (18.9%) and 30 (17.1%). While, CMV-PP65 Ag which was detected in 26 (14.9%) and 28 (16.0%) respectively (P < 0.0001).  High level of abnormal IL-33 was detected in 36 (20.6%) with 45 (25.7%) of abnormal IgE was determined in patients with asthma followed by 26 (14.9%) and 44 (25.1%) for abnormal levels of IL-33 and IgE respectively in patients with atherosclerosis. Furthermore, there was a positive significant association between the seropositivity of CMV-IgG and CMV-PP65 Ag with abnormal IgE and IL-33 levels in the pathogenesis of asthma and atherosclerosis (P < 0.0001), and impact of our study support the hypothesis that previous cytomegalovirus infection or early reactivation with unregulated IL-33 expression or high IgE level play a significant role in the pathogenesis of coronary heart diseases and asthma.