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Objectives Platelets have been proposed both as effector cells in the pathogenesis of SLE and as targets of autoimmune phenomena during the disease course. Thrombocytopenia has been reported in 20–40% of patients with SLE and may even precede the diagnosis by several years or decades. This study aimed to determine the prevalence and clinical characteristics of lupus patients with thrombocytopenia, and to evaluate its role as a potential prognostic factor.Methods We conducted a retrospective study over a 15-year period (January 2010 to December 2024), including patients with a confirmed diagnosis of SLE in the Internal Medicine Department at Mohammed VI University Hospital in Marrakesh.Results Of the 419 SLE cases collected, thrombocytopenia was reported in 119 patients (24.8%). The mean age was 35 years [range: 15–70], with a marked female predominance (F/M = 9). Thrombocytopenia was initially revealed by a hemorrhagic syndrome in 15.9% of cases, with 21% of patients having a platelet count below 20,000/mm 3. Across all manifestations, the mean SLEDAI score was higher in patients with thrombocytopenia (SLEDAI: 14.5) than in those without (SLEDAI: 9.7) (p < 0.0001). Thrombocytopenia was mainly associated with renal involvement, observed in 49.6% of affected patients (p = 0.023), and vascular involvement in 16.3% (p = 0.015). It was present in all patients with pulmonary involvement, though this was not statistically significant. Thrombocytopenia was isolated in 28 cases (23.5%), associated with anemia in 83 cases (69.7%, p = 0.03) and lymphopenia in 61 cases (51.2%, p = 0.11). Regarding immune profile, antinuclear antibodies, anti–double-stranded DNA antibodies, and low complement levels were reported in 94.0% (p = 0.41), 75.9% (p = 0.47), and 50% (p = 0.002) of these patients, respectively. Regarding treatment, 93.8% received antimalarials and 95.3% received systemic corticosteroids (oral or pulse therapy). Immunosuppressive and biologic therapies were mainly administered when hematologic involvement was associated with other systemic manifestations, except in two cases where rituximab was required for refractory thrombocytopenia.Conclusions Thrombocytopenia in SLE remains relatively common. Its reported association with severe systemic involvement and increased mortality makes it an independent prognostic factor and a warning sign, warranting careful monitoring to improve patient outcomes.