Background: Narcolepsy type 1 (NT1) is primarily caused by a malfunctioning immune system in which T-cells damage the hypothalamus. To elucidate the causal relationships between biomarkers in T-cells and NT1, we employed Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis utilizing genetically predicted T-cell traits to examine their effects on NT1. Genome-wide association study summary data were extracted from studies by Valeria (3,757 participants) for 211 T-cell traits, Ollila (6,073 cases and 84,856 controls) for NT1. The MR analysis was executed at two threshold levels. Inverse variance weighted, Wald ratio, weighted median, and MR-Egger regression methods were used for the MR analysis. Odds ratios (ORs) were calculated, and heterogeneity tests, as well as pleiotropy tests, were conducted. Results: After Bonferroni correction at the significant level (p < 1.18 x 10(-4)), a higher ratio of naive CD4(-) CD8(-) T-cells was identified as a risk factor for NT1 (OR = 10.50; 95% CI: 6.98, 15.90, p = 3.89 x10(-29)). Conversely, CD4 on HLA DR+ CD4(+) T cells (mean fluorescence intensity, MFI) exhibited a negative correlation with NT1. At nominally significant levels (p < 0.05) for both threshold levels, HVEM (herpesvirus entry mediator) on naive CD8(+) T cells (MFI) was suggested as a protective factor for NT1. Additionally, a higher ratio of CD25(++) CD45RA(-) CD4 not regulatory T cells, CD127 on CD45RA- CD4 not regulatory T cells (MFI), CD127 on CD28(+) CD4(+) T cells (MFI), CD3 on HLA DR+ T cells (MFI), and CD3 on HLA DR+ CD4(+) T cells (MFI) were suggested as risk factors for NT1. Conclusion: This study confirmed the causal effects of CD4(+) and CD8(+) T-cells on NT1 and found several novel T-cell-related characteristics.