Lisa wakes up one morning saddened. At school, she gets in trouble with her music teacher for improvising, and her gym teacher sends home a note to her parents saying she was reluctant to play dodgeball. At home, Homer and Bart pummel each other at video boxing, but despite Homer's attempts, he is unable to defeat Bart. Homer and Marge try to cheer Lisa up, but she is consumed with worry over all the suffering in the world. In her room, Lisa hears music coming from outside her window. She follows the music through town and meets Bleeding Gums Murphy, a soulful saxophonist playing the blues. Lisa learns about expressing herself through her music from him, only to be discovered and whisked away by Marge.
Homer goes to the arcade and enlists the help of a local video game wizard, while Marge takes Lisa to band practice. She tells Lisa to smile no matter how she feels inside, to suppress her emotions in order to be popular, and that happiness will follow. But when she sees Lisa hiding her true feelings and being taken advantage of by her classmates, Marge changes her tune and tells Lisa to be herself and her support helps Lisa to feel genuinely happy. When Homer returns home, he is about to defeat Bart in a rematch but Marge unplugs the game console to announce Lisa's recovery, while Bart declares his retirement as undefeated video boxing champ. Later, the Simpsons visit a jazz club to hear Bleeding Gums Murphy sing a blues number written by Lisa.