ABSTRACT: The GICE (Guttenberg Carbon Isotope Excursion) is a positive d13C excursion and a prominent feature of the Late Ordovician chemostratigraphic record. The GICE has been identified on different paleocontinents, and its cause is still unresolved. One explanation suggests that the GICE is the carbon isotopic expression of changes that occurred during the transition from an icehouse to greenhouse climate ~10 myr prior to the end Ordovician glaciation and mass extinction event. There are lithological and paleontological observations across this time interval that support cooling, but such evidence contradicts documented oxygen isotopic trends at low to middle latitudes that instead indicate warming during this interval. We measured neodymium isotopes, which are a weathering proxy and water mass tracer, in conodonts from the Upper Mississippi Valley to determine if changes in the global climate system might account for the lithologic and paleontologic changes observed across the GICE interval. The Nd isotopic values increase from -14.7 to -10.3 across 2 m of section up to the stratigraphic level of the Deicke K-bentonite. A decrease in Nd values occurs between the Deicke K-bentonite and the overlying Millbrig K-bentonite with values ranging from -16.2 to -18.5 across 8 m of section above the Millbrig K-bentonite. These results suggest high inputs due to weathering of proximal Precambrian shield rocks with lower Nd values high in the section, reflecting a regression (consistent with glacial growth) between the Millbrig and Deicke K-bentonites. However, a documented decrease in d18O values in the study area and stratigraphic evidence for a regional transgression conflict with scenarios invoking glaciation and regression at this time. Local tectonic quiescence during the GICE also precludes a tectonically driven regression as a source of increased nonradiogenic Nd weathering flux. Therefore, the decrease in Nd values in this stratigraphic interval is suggested to result from increased weathering rates driven by global climatic change and/or circulation changes that increased input of a nonradiogenic signature to the region. These findings imply that using Nd as a direct proxy for eustatic changes, as suggested in previous work, is complicated during periods of changing climate and weathering fluxes.