In neonates, renal vein thrombosis (RVT) is the second most common thrombosis.We report a case of antenatal bilateral RVT and we review the optimal therapeutic approaches. I, a male newborn was admitted in the Neonatal Intensive Care Unit of the Center for Maternity and Neonatology of Tunis (CMNT) for respiratory distress and gross hematuria. Initial laboratory work demonstrated renal impairment and Doppler renal ultrasound confirmed the diagnosis of bilateral RVT. Thrombophilia evaluation found a combined protein C and S deficiency. Thrombolysis was started with tissue plasminogen factor in association to anticoagulation with unfractionated heparin. Renal vein thrombosis in neonates is a rare condition with a high morbidity rate. Thrombotic conditions may be associated with more severe clinical presentations. Currently, there is a lack of consensus concerning the management of RVT.