Importance The epithelial barrier theory (EBT) proposes that epithelial barrier disruption is implicated in the development of skin, respiratory, gastrointestinal, and ocular diseases (epithelial barrier diseases, or EBDs). There is a need to better understand the relationship between seborrheic dermatitis and EBDs, and we hypothesize that seborrheic dermatitis, characterized by epithelial barrier dysfunction, is associated with increased frequency of other EBDs. Objective To explore the association between seborrheic dermatitis and EBDs. Design, Setting, and Participants This retrospective cohort study used a large US administrative claims database, which included data collected from multiple health care centers and patient care settings across the US from January 1, 2016, through June 30, 2022. This study consisted of patients aged 18 years and older at enrollment, with at least 1 year of continuous enrollment, and with a minimum of 2 visits on unique days to a medical professional. The mean (SD) patient follow-up time was 3.46 (1.80) years with a total follow-up of more than 70 million person-years. Individuals with missing data for demographic covariates, including age, sex, and division (ie, billing region), were excluded. Data were analyzed from January to September 2025. Exposures Diagnosis of seborrheic dermatitis at any point during the observation period. Main Outcomes and Measures Diagnosis of an EBD at any point during the observation period. Results Of 20 274 189 patients, 733 776 (3.62%) had seborrheic dermatitis (median [IQR] age, 62.63 [41.53-70.55] years; 54.7% female). Using adjusted models, seborrheic dermatitis was positively associated with atopic dermatitis (odds ratio [OR], 3.21; 95% CI, 3.18-3.24), alopecia areata (OR, 4.02; 95% CI, 3.93-4.11), contact dermatitis (OR, 2.25; 95% CI, 2.23-2.26), psoriasis (OR, 3.26; 95% CI, 3.23-3.29), rosacea (OR, 4.52; 95% CI, 4.49-4.56), hidradenitis suppurativa (OR, 1.63; 95% CI, 1.58-1.68), chronic spontaneous urticaria (OR, 1.35; 95% CI, 1.33-1.37), pemphigus vulgaris (OR, 1.48; 95% CI, 1.31-1.69), bullous pemphigoid (OR, 1.60; 95% CI, 1.51-1.70), rhinosinusitis (OR, 1.24; 95% CI, 1.24-1.25), celiac disease (OR, 1.36; 95% CI, 1.32-1.39), irritable bowel syndrome (OR, 1.32; 95% CI, 1.31-1.33), ocular allergy (OR, 1.39; 95% CI, 1.37-1.41), and dry eye (OR, 1.48; 95% CI, 1.48-1.49) and was negatively associated with chronic obstructive pulmonary disease (OR, 0.72; 95% CI, 0.71-0.72) and pulmonary hypertension (OR, 0.70; 95% CI, 0.69-0.71). Conclusions and Relevance These findings support the EBT as a shared driver in the pathogenesis of seborrheic dermatitis and other diverse EBDs and encourage further investigation into the underlying mechanisms of disease pathogenesis.