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Background/Objectives: Systemic lupus erythematosus (SLE) is frequently accompanied by psychological distress. Alexithymia, an impairment in identifying and describing emotions, has been reported in SLE, but its clinical and serological correlates remain insufficiently characterized. We aimed to estimate the prevalence of clinically significant alexithymia in SLE and to explore its clinical, laboratory, and coping-related correlates. Methods: In this cross-sectional observational study, adult outpatients fulfilling the 2019 ACR/EULAR SLE classification criteria were assessed at a tertiary referral centre (2024–2025). Alexithymia was measured using the Toronto Alexithymia Scale-20 (TAS-20), and clinically significant alexithymia was defined as a total score >60. Coping strategies were assessed with the 60-item COPE inventory (Italian version). Clinical indices (SLEDAI-2K, Lupus Low Disease Activity State (LLDAS), and SLICC/ACR Damage Index (SDI)), organ involvement, antiphospholipid syndrome (APS), selected autoantibodies, complement levels, and treatments were recorded. Group comparisons and exploratory logistic regression were performed. Results: Sixty-eight patients were included (94.1% female). Clinically significant alexithymia was present in 23.5%. In univariate analysis, alexithymia was more frequent among patients with APS. Alexithymic participants reported higher use of emotional venting and lower use of positive reinterpretation. In an exploratory multivariable logistic regression model, APS (adjusted OR 35.79, 95% CI 3.74–341.7), emotional venting (adjusted OR 1.684, 95% CI 1.162–2.44), and positive reinterpretation (adjusted OR 0.514, 95% CI 0.349–0.755) remained associated with alexithymia. Conclusions: Alexithymia was frequent in this SLE cohort and, in exploratory analyses, was associated with APS and specific coping patterns. These findings suggest that assessment of emotional processing and coping may provide complementary clinical information, particularly in patients with APS, but should be interpreted as associative and hypothesis-generating.