Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable degree of lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations. Minor salivary gland (MSG) lesions mainly consist of T and B cells, while antigen-presenting cells have been reported in heavy infiltrates. Evidence suggests that the infiltrate composition differs according to lesion severity; however, these differences are not well-defined. To investigate the differential distribution of the major infiltrating mononuclear cell (MNC) types in SS-lesions of variable severity, total-T, CD4(+)-T, CD8(+)-T, Treg, and B cell, macrophage (MPhi), interdigitating (iDC) and follicular dendritic cell (fDC), and natural-killer (NK)-cell incidence (%-total infiltrating MNC) was analyzed in MSG biopsies with mild (n = 11), intermediate (n = 13) or severe (n = 15) lesions. T cells, CD4(+)-T cells and Tregs, B lymphocytes, MPhis and iDCs were significantly different among MSG tissues with mild, intermediate or severe inflammatory lesions, while CD8(+)-T cell, fDC and NK cell incidence was not correlated with lesion severity. T cell, CD4(+)-T cell, T/B cell ratio and iDC incidence was negatively, whereas B cell and MPhi incidence was positively correlated with infiltration grade and biopsy focus score. Tregs predominated in intermediate lesions. Multivariate analysis revealed several associations between the incidence of each infiltrating MNC-type and disease manifestations, implying an involvement of local immune responses in systemic disease features. Our findings support that the distribution of infiltrating MNCs at the SS-lesions varies according to lesion severity and correlates with disease manifestations. The significance of this differential distribution and the underlying aetiopathogenic factors need to be elucidated.