Deproteinized whey (DPW) is obtained during ultrafiltration of whey and it is processed into a non-hygroscopic and free-flowing DPW powder. DPW powders may undergo changes such as caking and Maillard browning during storage due to its high lactose content. This study investigated the effect of temperature and relative humidity (RH) on the physical, chemical, and thermal properties of DPW powders. Six DPW powders were obtained from a commercial manufacturer with varying protein contents ranging from 2.47 to 3.42%. The water activity (a_w), color, pH, titratable acidity, and fluorescence of advanced Maillard products and soluble tryptophan (FAST index) were determined for the fresh powders. The a_w of the fresh powders was in the range 0.222 to 0.285. It was observed that as the protein content increased the titratable acidity increased in the fresh powders. The lightness (L*) values ranged from 86.7 to 88.8 and the FAST index values ranged from 60.83 to 153.92 for the fresh powders. The DPW powders were stored over saturated salt solutions with RH (11.2, 22.6, 43.8 and 52.9%) and temperature (25 and 40°C) for 1 mo. The color and FAST index were determined for the powders after storage. It was observed that temperature, RH, and their interactions significantly influenced (P < 0.05) color and FAST index. We found that the L* values decreased on storage and ranged from 51.76 to 80.81. Also, FAST index values increased with storage ranging from 67.23 to 879.43. The Maillard browning was studied using front face fluorescence spectroscopy (excitation: 360 nm and emission: 380 to 480 nm) and the emission spectra showed a broad peak with a maximum around 437 nm for the fresh and stored powders. The thermal properties of DPW powders were determined with differential scanning calorimetry and a dehydration endothermic peak at around 142°C was observed. Overall, the DPW powders stored at RH 43.8 and 52.9% at 25 and 40°C showed poor quality characteristics as indicated by FAST index and color.