Tight glucose monitoring is essential for the reduction of diabetic complications. This research investigated the changes of absorption spectra observed in serum at three prominent glucose absorption peaks in the middle infrared using a demountable liquid, transmission cell. Two frequencies of light were used to determine the glucose absorption: one at 1193 cm-1 to determine the background water absorption and the other at one of the characteristic peaks (1035, 1080, and 1109 cm-1). The peak at 1035 cm-1 was best for quantitative determination with a standard of error of 20.6 mg/dl (1.1 mmol/L). While interference from other serum constituents could cause problems, urea and albumin-two constituents known to have close absorption peaks-were determined to have no effect on the ability to determine the glucose levels at 1035 cm-1. © 2002 Society of Photo-Optical Instrumentation Engineers.