Cobaloximes are popular H 2 evolution molecular catalysts, but have so far mainly been studied in non-aqueous conditions. We show here that they are also valuable for the design of artificial hydrogenases for application in neutral aqueous solutions and report on the preparation of two well-defined biohybrid species via the binding of two cobaloxime moieties {Co(dmgH) 2 } and {Co(dmgBF 2 ) 2 }(dmgH 2 = dimethylglyoxime) to apo Sperm-whale myoglobin (SwMb). All spectroscopic data confirm that the cobaloxime moieties are inserted within the binding pocket of the SwMb protein and are coordinated to a histidine residue in axial position of the cobalt complex, resulting in thermodynamically stable complexes. QC/MM docking calculations indicated coordination preference for His93 over the other histidine residue (His64) present in the vicinity. Interestingly, the redox activity of the cobalt centers is retained in both biohybrids which provides them with catalytic activity for H 2 evolution in near neutral aqueous conditions.