Abstract We present observations using the Northern Extended Millimetre Array (NOEMA) of CO and H 2 O emission lines and the underlying dust continuum in two quasars at z ∼ 6, i.e., P215−16 at z = 5.78 and J1429+5447 at z = 6.18. Notably, among all published CO spectral line energy distributions (SLEDs) of quasars at z ∼ 6, the two systems reveal the highest and the lowest CO levels of excitation, respectively. Our radiative transfer modeling of the CO SLED of P215−16 suggests that the molecular gas heated by active galactic nuclei could be a plausible origin for the high CO excitation. For J1429+5447, we obtain the first well-sampled CO SLED (from transitions from 2−1 to 10−9) of a radio-loud quasar at z ≳ 6. Analysis of the CO SLED suggests that a component from a single photodissociation region could explain the CO excitation in the radio-loud quasar J1429+5447. This work highlights the utility of the CO SLED in uncovering the properties of the interstellar medium in these young quasar–starburst systems at the highest redshift. The diversity of the CO SLEDs reveals the complexities in gas conditions and excitation mechanisms at their early evolutionary stage.