Modified diatomite (acid treated and ZrO2-coated diatomite) coated by nano copper and titanium mixed oxides was used to investigate the catalytic oxidation of carbon monoxide. The prepared catalysts were characterized by Brunauer–Emmett–Teller (BET) surface area, field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), temperature-programmed reduction (TPR), porosimetry, and X-ray photoelectron spectroscopy (XPS). Catalytic behavior for CO oxidation was studied in different conditions in a tubular reactor packed with catalyst. The variation of catalytic activity of the prepared composite catalysts with different molar fractions of CuO and TiO2 for CO oxidation in different reaction temperatures was investigated. The catalytic activity of catalyst was dependent on the concentration of coated catalyst over diatomite, reaction temperature and retention time. The results illustrated that diatomite is the promising candidate for catalyst support due to its unique characteristics. It was found that CO conversion of 100% can be achieved at 220 °C over catalyst with 70 mol% CuO and 30 mol% TiO2 content.