The spatial variability of nitrogen (N) and the spectral response of crops to N have resulted in the utilization of canopy reflectance indices to drive on-the-go, variable rate applications of fertilizer N (VRN).  However, spectral response to variety and available potassium (K) are not typically considered in the development of these indices. Response of each index to these variables must be considered to prevent inaccurate N applications and subsequent environmental and financial repercussions.  The objective of this research was to examine the response of two contrasting indices to variety and available K.  A randomized strip, complete block trial with five replications was conducted in 2012 at the Lon Mann Cotton Research Center in Marianna, AR.  Prior to planting, soil samples were taken from each plot and analyzed.  Treatments consisted of an untreated check, 30, 60, and 90 lb applied K₂O/acre to Phytogen 499 WRF, Stoneville 5458 B2RF, and DeltaPine 0912 B2RF varieties.  Reflectance measurements were taken by the Crop Circle ACS-470 (Holland Scientific Inc., Lincoln, NE).  Measured wavelengths were used to calculate the Normalized Difference Vegetation Index (NDVI) and the Canopy Chlorophyll Content Index (CCCI).  Interaction effects between available K and variety on NDVI were significant (p<0.10), however, CCCI was only significantly affected by variety (p<0.05).  Results suggest NDVI based algorithms have the potential to recommend excessive fertilizer N quantities when K deficiencies are present.  In contrast, CCCI does not appear to be susceptible to such errors. Still, both indices will require some correctional factor to adjust for varietal effects.