Chlorine monoxide (ClO) is the key species for anthropogenic ozone losses in the middle atmosphere. We observed ClO diurnal variations using the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on the International Space Station, which has a non-sun-synchronous orbit. This includes the first global observations of the ClO diurnal variation from the stratosphere up to the mesosphere. The observation of mesospheric ClO was possible due to 10–20 times better signal-to-noise (S/N) ratio of the spectra than those of past or ongoing microwave/submillimeter-wave limb-emission sounders. We performed a quantitative error analysis for the strato- and mesospheric ClO from the Level-2 research (L2r) product version 2.1.5 taking into account all possible contributions of errors, i.e. errors due to spectrum noise, smoothing, and uncertainties in radiative transfer model and instrument functions. The SMILES L2r v2.1.5 ClO data are useful over the range from 0.01 and 100 hPa with a total error estimate of 10–30 pptv (about 10%) with averaging 100 profiles. The SMILES ClO vertical resolution is 3–5 km and 5–8 km for the stratosphere and mesosphere, respectively. The SMILES observations reproduced the diurnal variation of stratospheric ClO, with peak values at midday, observed previously by the Microwave Limb Sounder on the Upper Atmosphere Research Satellite (UARS/MLS). Mesospheric ClO demonstrated an opposite diurnal behavior, with nighttime values being larger than daytime values. A ClO enhancement of about 100 pptv was observed at 0.02 to 0.01 hPa (about 70–80 km) for 50° N–65° N from January–February 2010. The performance of SMILES ClO observations opens up new opportunities to investigate ClO up to the mesopause.