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Signal joint T cell receptor excision circles (<i>sjTRECs</i>) are a promising marker for age estimation and immunosenescence in different ethnic groups. Several limitations are expected to overshadow their use as accurate markers for age prediction. The current study was conducted to determine the influence of immunologic disorders, such as autoimmune diseases and COVID-19, on the accuracy of <i>sjTRECs</i> as molecular markers for age estimation and immunosenescence among living Egyptians. Peripheral blood <i>sjTRECs</i> level was measured by qPCR in 90 autoimmune patients, 58 COVID-19 patients, and 85 healthy controls. The mean dCt values were significantly (<i>p</i> = 0.0002) different between the three groups, with the highest values in healthy subjects, followed by autoimmune and COVID-19 patients. A significant negative correlation was identified between the <i>sjTRECs</i> levels and ages in all studied cases. There were significant positive correlations between chronological age and predicted age for healthy individuals, autoimmune, and COVID-19 patients with mean absolute deviations (MAD) of 9.40, 11.04, and 9.71, respectively. The two patients’ groups exhibited early immunosenescence, which was more noticeable among the young adults with COVID-19 and autoimmune patients of age range (18–49 years). Autoimmunity may represent a critical factor impacting the accuracy of <i>sjTRECs</i> quantitation for age prediction.