Objectives: Inflammation and serum oxidative stress (OS) are important components in heart failure (HF) deterioration. In this study we tested the hypothesis that an increase in patients’ sera OS levels is associated with acute HF (AHF) readmissions. Methods: Thirty consecutive patients (mean age 71 ± 10 years) admitted with AHF were included in the study. Serum OS in these patients was measured in-hospital and repeatedly after discharge over a period of 8 weeks of follow-up in which we reordered patients’ HF readmissions. Of the 30 patients, 13 (43%) were readmitted (RAD group) and 17 (57%) did not require readmission (NRAD group). Results: OS levels before discharge from the first hospital admission in the 2 groups were similar (p = 0.84 and p = 0.56, respectively). However, using repeated measures ANOVA, we found that the interaction between the time points and the 2 groups of patients (RAD and NRAD) was statistically significant (p = 0.037). It is important to note that OS serum levels were more predictive of HF readmissions than were repeated simultaneous serum measurements of NT-proBNP (p = 0.97). Conclusions: Increased OS levels in AHF patients, after they have been discharged from the hospital, are associated with higher HF readmission rates. In AHF, OS is a dynamic parameter associated with HF deterioration.