In a pilot study, we found that the NIRS measurements were highly variable and dramatically decreased or disappeared sporadically while monitoring gastro-intestinal (GI) StO2 on preterm neonates. We hypothesized that the light absorption characteristics of different neonatal and infant stool types may be interfering with NIRS GI measurements. Methods: Meconium, transitional, and mature stool samples collected from preterm neonates and older infants (ranging from a few days to weeks in age) were analyzed by a bench-top spectrometer to measure light absorbance in the near infrared range (650-950 nm). Results: Some meconium and transitional stool samples were noted to have a more marked increase in light absorbance as wavelength decreases towards 650 nm, when compared to more mature stools. When compared to the light absorbance spectra of deoxy-hemoglobin (Hb) and oxy-hemoglobin (HbO2), there is a high potential that Hb and HbO2 may be erroneously calculated, resulting in falsely low GI StO2. Discussion: Meconium and green colored transitional stools demonstrate a light absorbance spectra that may interfere with NIRS GI measurements, possibly due to their higher biliverdin content, which exhibits a broad spectral absorption peak at 660 nm. Caution is warranted in interpreting GI StO2 NIRS results in neonates still passing meconium and transitional stools until NIRS-based tissue oximeters to measure GI StO2 can compensate for the presence of these stool types.