Here, we report that structural modification of the nitroxide ring can cause a conformational shift to provide the first example of nitroxides in a fully closed conformation (Figure ). The additional steric shielding obtained through this strategy results in a dramatic increase in the stability of these nitroxides towards reduction by ascorbate. Moreover, the beneficial Tm of spirocyclic systems is largely preserved, resulting in a scaffold that finds a balance between improved stability and beneficial relaxation properties. These findings are of great significance for the future design of new nitroxide-based spin labels and imaging agents.