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Objectives Systemic Lupus Erythematosus (SLE) is an autoimmune disease driven by B-cell dysregulation. Rituximab (RTX) depletes B cells through complement-dependent cytotoxicity (CDC). Given that many SLE patients have hypocomplementemia (low serum C3 and/or C4) due to ongoing complement activation, this study aimed to determine whether complement levels at the start of RTX treatment influence clinical response and outcomes.Methods All consecutive SLE patients treated with RTX in our Unit and who fulfilled the 2019 ACR/EULAR classification criteria were included. Patients were grouped as having low complement (LowC) or normal complement (NormC) at treatment initiation. The primary endpoint was clinical response (CR) at 12 months, defined by a decrease in SLEDAI-2K =>4 points, no A and only one B domain in BILAG, and a prednisolone dose<=7.5mg/day. Secondary outcomes included achievement of lupus low-disease activity state (LLDAS) at 12 months, time to first flare, and prednisolone dose at 12 months.Results Of 48 RTX-treated patients, 46 were included, median age 32 (25-39) years; 85% female. RTX was started at 37 (9-160) months after diagnosis, and patients were followed for a median of 68 (30-110) months. Indication for RTX included refractory SLE (n=20), immune cytopenia (n=13), neuropsychiatric lupus (n=5), and lupus nephritis (n=8). Twenty-six patients (57%) had low complement at baseline. Most received concomitant immunosuppressants (61%) and high-dose corticosteroids (=>20mg/day, 72%). Sixteen patients (35%) experienced 21 flares during follow-up, with a median time to first flare of 12 (4-40) months after RTX.At 12 months, clinical response rates did not differ significantly between groups (58% in LowC vs 75% in NormC, p=0.182). Similarly, LLDAS was achieved in 54% of LowC vs 75% of NormC patients (p=0.122). However, LowC patients had significantly shorter time-to-flare (figure 1, median 7 vs 53 months; HR 3.82, 95% CI 1.06–13.8, p=0.041) and higher mean prednisolone doses at 12 months (7.7 ± 1.0 mg vs 5.4 ± 0.6 mg, p=0.045).Abstract PO:05:147 Figure 1Conclusions Although baseline hypocomplementemia did not affect short-term clinical response to RTX, it was associated with increased risk of flare and higher corticosteroid requirements. These findings suggest complement status may influence long-term RTX response and should be further explored in larger cohorts.