Much is known about the effect of odors on mood, cognition and behavior, but little is known about the relationship between odors and well-being. We investigated the neural processing of odors with different degrees of association with well-being (WB) through two large independent datasets. The study encompassed pre-testing and fMRI. During pre-testing, 100 and 80 (studies 1 and 2) young, healthy subjects participated, rating intensity, valence, and WB association for 14 (study 1) and 8 (study 2) different odors. Pre-testing resulted in the selection of two odors with high WB association (WB-associated) and two odors with lower WB association (neutral odors) for each study. Odors were delivered intranasally to the subjects who underwent fMRI scanning (44 and 41 subjects, respectively, for studies 1 and 2). We assessed brain activity for subjects when they experienced WB-associated versus neutral odors. In study 1, WB-associated odors showed increased activation in the right angular gyrus whereas in study 2, increased activity in the left angular gyrus existed, together with increased activity in the anterior cingulate cortex and posterior orbitofrontal cortex. The increased activity of higher-order cognitive and emotional regions during the processing of WB-associated odors in the two independent studies suggests a role of odors in influencing individual well-being. Moreover, the consistent activation of the angular gyrus might suggest its key role in shifting attention toward relevant emotional stimuli.