Vulvodynia, impacts up to 8% of women by age 40, and is hypothesized to manifest through an altered immune-inflammatory response. To test this hypothesis, we identified all women born in Sweden between 1973 and 1996 diagnosed with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) between 2001 and 2018. We matched each case to two women from the same birth year with no vulvar pain ICD codes. As a proxy for immune dysfunction, we used Swedish Registry data to capture 1) immunodeficiencies, 2) single organ and multiorgan autoimmune conditions, 3) allergy and atopies, and 4) malignancies involving immune cells across the life course. Women with vulvodynia, vaginismus or both were more likely to experience immune deficiencies (OR 1.8, 95% CI, 1.2–2.8), single organ (OR 1.4, 95% CI, 1.2–1.6) and/or multi-organ (OR 1.6, 95% CI, 1.3–1.9) immune disorders, and allergy/atopy conditions (OR 1.7, 95% CI, 1.6–1.8) compared to controls. We observed greater risk with increasing numbers of unique immune related conditions (1 code: OR = 1.6, 95% CI, 1.5–1.7; 2 codes: OR = 2.4, 95% CI, 2.1–2.9; 3 or more codes: OR = 2.9, 1.6–5.4). These findings suggest that women with vulvodynia may have a more compromised immune system either at birth or at points across the life course than women with no vulvar pain history.