In the cell, enzymes are almost always spatially confined in crowded and tightly controlled cellular compartments. The entrapment of enzymes in artificial nanoreactors as biomimetic systems can be expected to contribute to the understanding of the activity and the interactions of enzymes in confined spaces. The capsid of the Cowpea Chlorotic Mottle virus (CCMV) represents such an artificial nanoreactor that can be used to encapsulate multiple proteins in its interior. Employing a controlled encapsulation process we are able to load a precise number of proteins (Pseudozyma antarctica lipase B and EGFP) into the CCMV capsid and to study their activity. In the case of the enzyme, our results indicate that the apparent overall reaction rate increases upon encapsulation and is almost independent of the number of enzymes in the capsid. These observation are the result of the extremely high confinement molarity of the enzyme inside the capsid (Mconf = ∼ 1 mM) leading to very rapid formation of the enzyme–substrate complex. These results highlight the importance of small volumes for efficient multi-enzyme cascade catalysis.