The inertness of metal clusters in air is important for their application to novel materials and catalysts. The adsorption reactivity of copper clusters with O-2 has been discussed in connection with the electronic structure of clusters because of its importance in electron transfer from the cluster to O-2. Mass spectrometry was used to observe the reaction of Cu-n(+) + O-2 (n = 13-60) in the gas phase. For O-2 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 Cu-15(+), with 14 valence electrons was related to the large HOMO-LUMO gap predicted for the oblate Cu-15(+) structure. The Clemenger-Nilsson model was used to predict that the electronic subshell of oblate Cu-49(+) with 48 electrons was closed. This electronic shell closing of Cu-49(+) corresponds to the inertness for O-2 adsorption.