The inertness of metal clusters in air is important for their application to novel materials and catalysts. The adsorption reactivity of copper clusters with O2 has been discussed in connection with the electronic structure of clusters because of its importance in electron transfer from the cluster to O2. Mass spectrometry was used to observe the reaction of Cu n+ + O2 ( n = 13-60) in the gas phase. For O2 adsorption on Cu n+, the relative rate constants of the n = 15, 21, 41, and 49 clusters were clearly lower than those with other n. Theoretical calculations indicated that the inertness of Cu15+ with 14 valence electrons was related to the large HOMO-LUMO gap predicted for the oblate Cu15+ structure. The Clemenger-Nilsson model was used to predict that the electronic subshell of oblate Cu49+ with 48 electrons was closed. This electronic shell closing of Cu49+ corresponds to the inertness for O2 adsorption.