Cysteine plays an essential role in maintaining cellular redox homeostasis and perturbations in cysteine concentration are associated with cardiovascular disease, liver disease, and cancer. 19F MRI is a promising modality for detecting cysteine in biology due to its high tissue penetration and negligible biological background signal. Herein we report fluorinated macrocyclic copper complexes that display a 19F NMR/MRI turn-on response following reduction of the Cu(ii) complexes by cysteine. The reactivity with cysteine was studied by monitoring the appearance of a robust diamagnetic 19F signal following addition of cysteine in conjunction with UV-vis and EPR spectroscopies. Importantly, complexes with -CH2CF3 tags display good water solubility. Studies with this complex in HeLa cells demonstrate the applicability of these probes to detect cysteine in complex biological environments.