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A major challenge for a wearable dialysis device is removal of urea, as urea is difficult to adsorb while daily production is very high. Electro-oxidation (EO) seems attractive because electrodes are durable, small, and inexpensive. We studied the efficacy of urea oxidation, generation of chlorine by-products, and their removal by activated carbon (AC). EO units were designed. Three electrode materials (platinum, ruthenium oxide, and graphite) were compared in single pass experiments using urea in saline solution. Chlorine removal by AC in series with EO by graphite electrodes was tested. Finally, urea-spiked bovine blood was dialyzed and dialysate was recirculated in a dialysate circuit with AC in series with an EO unit containing graphite electrodes. Platinum electrodes degraded more urea (21 ± 2 mmol/h) than ruthenium oxide (13 ± 2 mmol/h) or graphite electrodes (13 ± 1 mmol/h). Chlorine generation was much lower with graphite (13 ± 4 mg/h) than with platinum (231 ± 22 mg/h) or ruthenium oxide electrodes (129 ± 12 mg/h). Platinum and ruthenium oxide electrodes released platinum (4.1 [3.9-8.1] umol/h) and ruthenium (83 [77-107] nmol/h), respectively. AC potently reduced dialysate chlorine levels to < 0.10 mg/L. Urea was removed from blood by EO at constant rate (9.5 ± 1.0 mmol/h). EO by graphite electrodes combined with AC shows promising urea removal and chlorine release complying with Association for the Advancement of Medical Instrumentation standards, and may be worth further exploring for dialysate regeneration in a wearable system.