Lactose-free probiotic powders were obtained by mixing Bifidobacterium BB-12 suspensions with lactose-free milk powder or lactose-free milk powder and prebiotics (inulin or oligofructose). A thorough investigation was performed to know their water sorption properties and physical and thermal characteristics. By evaluating the water sorption properties, the Peleg model fitted well to the experimental sorption data, showing that the equilibrium moisture content of powders increased as the relative humidity increased. The isotherm found for all samples was a Type III Isotherm, commonly observed in most foods. For both morphology and particle size, the use of different carrier agents affected these properties; however, all the spray-dried powders presented good size to be added in food products. X-ray diffraction and Raman spectroscopy showed us amorphous structure for all powders, and typical bands of the milk constituents and sugars, respectively. Regarding the spray-dried powders thermal properties, it was possible to confirm that the addition of prebiotics gave higher thermal stability, highlighting the sample produced with inulin. We concluded that a good quality of lactose-free milk based probiotic powder could be obtained using spray drying technique, with great potential to be applied in lactose-free dairy products.