Because of the nontoxicity, low cost, and versatility, CuO-functionalized materials have received much attention. Their performances are intensely dependent on the dispersion state of CuO. Herein we report a strategy to promote the dispersion of CuO by combining the confinement effect and guest-host interaction modulation. The confined spaces are inherent in as-prepared mesoporous silica SBA-15 (AS) between silica walls and templates, and Al is in situ incorporated into AS, yielding Al-AS with enhanced guest-host interaction. Our results show that, by using Al-AS as the support, up to 7 mmol.g(-1) (35.9 wt %) of CuO can be dispersed, while aggregation of CuO occurs on Al-CS (Al-doped calcined SBA-15 without confined spaces) and AS (without strong guest-host interaction) as well as serious aggregation on the traditional support CS with neither confined spaces nor strong guest-host interaction. Such a dispersion amount is obviously higher than CuO supported on various materials prepared by different methods reported up to now. We also demonstrate that the CuO-containing Al-AS materials exhibit better CO adsorption performances than CuO-containing Al-CS, AS, and CS counterparts with regard to capacity and selectivity.