Background <p>Lyme disease is a tick-borne illness that can result in a spectrum of musculoskeletal complications, ranging from infection-related arthritis to post-infectious, immune-mediated conditions. Although prior reports have linked Lyme disease to systemic autoimmune diseases, such as rheumatoid arthritis and psoriatic arthritis, non-radiographic axial spondyloarthritis (nr-axSpA) has not previously been described following Lyme disease.</p> Case presentation <p>A previously healthy patient developed monoarthritis of the ankle, with inflammatory synovial fluid and a positive Lyme Western blot, consistent with Lyme arthritis. Symptoms resolved after antimicrobial therapy. However, he subsequently developed new-onset inflammatory back pain, with symptoms persisting despite several courses of antibiotics. Examination revealed sacroiliac joint tenderness and a positive Flexion Abduction and External Rotation (FABER) test. Imaging demonstrated bilateral sacroiliitis, with multifocal bone marrow edema and subcortical erosions on MRI. HLA-B27 was positive, meeting classification criteria for nr-axSpA. Treatment with Adalimumab led to marked clinical improvement.</p> Discussion <p>Previous studies have described sacroiliitis in the context of active infection, though this case represents a novel association between Lyme disease and nr-axSpA. This case suggests that Lyme disease may be a potential trigger for nr-axSpA in genetically predisposed individuals and expands the spectrum of infection-associated autoimmunity. Clinicians should consider nr-axSpA in patients with persistent inflammatory back pain following Lyme disease.</p>