The effect of casein (CAS) and inulin (INUL), at ratios commonly found during infant formula processing, on the conformational changes of whey proteins (WP) was investigated. Model systems were prepared as aqueous dispersions of WP isolate alone or with calcium caseinate and/or INUL, and heated for 30 min at 66, 70 or 75 Celsius. Heat treatment of WP induced denaturation and aggregation. Solubility of WP system decreased by 25% when heated at 75 Celsius. Upon heating, the presence of CAS did not prevent WP denaturation, but increased protein solubility up to 100% in WP–CAS system and prevented aggregation. INUL affected the secondary structure of WP and increased the denaturation temperature, although it did not prevent aggregation nor solubility loss at 75 Celsius. In conclusion, presence of CAS prevented aggregation and solubility loss of WP during heating while INUL induced WP conformational changes impacting the denaturation stage.