This study reports an investigation of the concept, application and performance of a novel bioelectrochemical nitritation-anammox microbial desalination cell (MDC) for resource-efficient wastewater treatment and desalination. Two configurations of anammox MDCs (anaerobic-anammox cathode MDC (AnA
mox
MDC) and nitration-anammox cathode MDC (NiA
mox
MDC)) were compared with an air cathode MDC (CMDC), operated in fed-batch mode. Results from this study showed that the maximum power density produced by NiA
mox
MDC (1,007 mW/m
3
) was higher than that of AnA
mox
MDC (444 mW/m
3
) and CMDC (952 mW/m
3
). More than 92% of ammonium-nitrogen (NH
4
+
-N) removal was achieved in NiA
mox
MDC, significantly higher than AnA
mox
MDC (84%) and CMDC (77%). The NiA
mox
MDC performed better than CMDC and AnA
mox
MDC in terms of power density, COD removal and salt removal in desalination chamber. In addition, cyclic voltammetry analysis of anammox cathode showed a redox peak centered at −140 mV Vs Ag/AgCl confirming the catalytic activity of anammox bacteria towards the electron transfer process. Further, net energy balance of the NiA
mox
MDC was the highest (NiA
mox
MDC-0.022 kWh/m
3
>CMDC-0.019 kWh/m
3
>AnA
mox
MDC-0.021 kWh/m
3
) among the three configurations. This study demonstrated, for the first time, a N-E-W synergy for resource-efficient wastewater treatment using nitritation-anammox process.