Objective: Smoking cessation is associated with improved health and reduced risk of disease. Understanding specific factors that are associated with smoking cessation is important both for identifying those who may have the greatest difficulty quitting smoking and tailoring smoking cessation interventions accordingly. Low positive affect/anhedonia, a key transdiagnostic symptom of several psychiatric disorders, is associated with lower levels of smoking cessation in the general population, but to date, few studies have examined factors influencing smoking cessation among Spanish-speaking Mexican-American smokers. Methods: The current study examined whether low positive affect/anhedonia was inversely related to cessation status across 3 time points among Spanish-speaking Mexican-American smokers (N = 199) who were making a smoking quit attempt. Results: Using multilevel modeling, the between-person low positive affect/anhedonia score was found to be inversely associated with smoking at quit day, 3 and 26 weeks after quit while controlling for relevant covariates (i.e., age, gender, education, income, relationship status, heaviness of smoking index) but not when controlling for other symptoms of depression. Conclusions: Contrary to prior research, the results of this study did not confirm the unique predictive role of low positive affect/anhedonia among Mexican Americans, suggesting that risk factors for this group may be different from other populations and cessation approaches may also need to differ.