Cutaneous Lupus Erythematosus (CLE) encompasses a spectrum of skin manifestations of lupus, all of which are characterized by interface dermatitis and autoantibody deposition. Understanding the pathogenesis is critical to developing new treatments and for determining which patients are at risk for developing systemic disease. Prior studies from our laboratories using archived CLE skin biopsies and our novel CLE mouse model revealed significant upregulation of IFN signatures including the CXCR3 chemokine system in whole tissue. Here, we used a novel blister biopsy technique to sample interstitial skin fluid from CLE patients to perform single cell RNA sequencing (scRNAseq) and high parameter flow cytometry (Cytek Aurora) to confirm expression of key molecules. Single cell RNAseq analysis of skin from human CLE patients revealed upregulation of the CXCR3 ligands CXCL9 and CXCL10 in lesional skin by keratinocytes, macrophages and T cells themselves. In concert, we found high expression of CXCR3 on both human and mouse T cells and other immune cells in lesional CLE by flow cytometry. Treating CLE mice with CXCR3 blocking antibodies did not significantly impact the frequency of antigen-specific T cells in the skin, but did prevent worsening of skin disease in mice. Surprisingly, CXCR3 antibody treatment also reduced spleen weight and autoantibody titers. Taken together, our data indicate that the CXCR3 chemokine axis contributes to both skin and lymphoid pathogenesis in the CLE mouse model, and indicate that similar pathways of migration exist in CLE patients. Future studies will focus on translating related therapies for CLE patients.