The serum levels of beta interferon (IFN-β) were evaluated in clinical samples taken in the acute phase of dengue fever for 107 patients during the 2011 dengue outbreak in Yucatán, México. Dengue diagnoses were confirmed by NS1 or IgM/IgG serology in all patients. Average serum IFN-β levels in patients with dengue fever without warning signs (n = 53) were 140 pg/ml, and 105 pg/ml for patients with warning signs (n = 54). There was no statistically significant difference between IFN-β levels for the two groups (Mann-Whitney U Test P > 0.05) and no association with warning or mild signs (OR: 0.57; 95%CI: 0.26-1.22) was indicated. Thrombocytopenia was the most prevalent warning sign (91%) in one group of patients (49) with mean 113 pg/ml IFN-β levels. In contrast, the patients without thrombocytopenia (50) had 126 pg/ml of IFN-β, but this level was not statistically significant (Mann-Whitney U Test P > 0.05). The average levels of IFN-β were also found to have statistically similar results, using the 1997 WHO classification system. The amount of IFN-β at 1-3, 4-6, and 7-9 days after onset of illness, however, did show significant differences (ANOVA P = 0.038) between patients for the 1-3 and 4-6 days pair (Scheffe post-hoc P = 0.043). These results suggest that serum levels of IFN-β do not correlate well with the severity of dengue illness, but there is a clear association between changes in IFN-β levels and the days of evolution during the acute phase of the disease. © 2015 Wiley Periodicals, Inc.