Background: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length and immune cells remains unclear. Methods: The two-sample Mendelian randomization (MR) analysis was conducted to elucidate the potential causal relationship. The genetic data of telomere length and the quantity of lymphocytes were obtained from the Genome-Wide Association Study. The inverse variance-weighted method was used to estimate the effects primarily and another four methods were as a supplement. Relevant sensitivity analysis was used to test the results. Results: The IVW method showed a significant correlation between telomere length and the percentage of T lymphocytes (OR: 1.222, 95% CI: 1.014-1.472, P = 0.035), indicating that short telomere length significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter telomere length may primarily lead to a lower proportion of Natural Killer T cells (OR: 1.574, 95% CI: 1.281-1.935, P < 0.001). Analysis of B cell subsets revealed that shorter telomere length may be associated with a higher proportion of Naive-mature B cells, and a lower proportion of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings. Conclusion: In summary, a causal relationship existed between telomere length and the quantity and differentiation of immune cells. Specifically, genetically predicted shorter telomere length was found to increase the risk of occurrence of immunosuppression and immunodeficiency.