Final answer:
Opal is most upset when Winn-Dixie runs away because she feels a deep connection and love for him.
Step-by-step explanation:
In the book 'Because of Winn-Dixie,' Opal is most upset when Winn-Dixie runs away because she feels a deep connection and love for him. Opal sees Winn-Dixie as a loyal and comforting friend who helps her feel less lonely in a new town. When he runs away, Opal is worried about losing that friendship and support.