Angiogenesis and microvascular endothelial injury play a role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been investigated in few studies in SLE with no reports targeting SLE with cutaneous manifestations. To evaluate NFC changes and VEGF serum level in relation to disease activity in SLE patients with versus without cutaneous manifestations. Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC changes and were related to disease activity. VEGF serum levels were significantly higher in patients than controls (median and interquartile range [IQR]: 2110.77, 471.09–4714.30 vs 60.00, 14–366, respectively, P < 0.0001). VEGF cut-off value to predict SLE patients was more than 293 and to detect moderate and severe SLE activity was more than 422 pg/mL and more than 3800 pg/mL, respectively. Serum VEGF levels increased with increased disease activity (P < 0.05). It was significantly higher in group I than group II (median and IQR: 2624.74, 1801.39–4141.70 vs 862.50, 180–2426.95, respectively, P < 0.05). Mean serum VEGF was significantly higher with NFC score 3 than 1 (P = 0.008). NFC score and SLE activity were significantly associated in patients (P < 0.05). Serum VEGF is significantly elevated in SLE patients with cutaneous manifestations and its cut-off values to detect different activity grades of SLE are identified. Abnormalities in NFC reflect the extent of microvascular involvement in SLE.