Chronic lymphocytic leukaemia (CLL) is a common type of leukaemia characterised by an abnormal increase in T-cell count. T-helper cytokines were reported to stimulate the survival and proliferation of CLL cells and could be correlated with disease progression. This study aims to study the possible inter-regulation and correlation between IL-22 and CD38 in CLL patients. It was carried out on newly diagnosed B-CLL patients and healthy controls. Routine laboratory investigations were carried out for all subjects. Haematological laboratory investigations were performed for all subjects, these included CD19, CD38 and interleukin-22 (IL-22) absolute and percentage counts. CLL patients showed a significant (P<0.05) increase in CD19, CD38 and IL- 22 absolute and percentage counts by comparison to the healthy control subjects. 25% of CLL patients showed positive CD38 expression. Interestingly, IL-22 percentages showed an association with CD38 expression. IL-22 percentage showed an increase in patients with high CD38 expression and a decrease in patients with low CD38 expression. Moreover, there was a significant (P<0.05) positive correlation between CD38 and IL-22 with Pearson's correlation coefficient (r=0.621). Thus, CD38 and IL-22 could act in synergy to maintain CLL cell survival and proliferation and could be used as diagnostic and prognostic markers.