Background: Recent evidence suggest that energy distribution during the daytimecould be a potential determinant for the development of metabolic syndrome (MetS). Objective: To cross-sectionally assess the association between breakfast size and the prevalence of MetS in Spanish adults. Methods: Our study included a subset of 3644 participants from the European Prospective Investigation into Cancer and Nutrition Spain study recontacted between 2017–2018. Information on diet, sociodemographic, lifestyle, sleep quality, and chronotype was collected using standardized questionnaires, while anthropometric and blood pressure data were measured in a face-to-face personal interview by a nurse. MetS was defined according to the Adult Treatment Panel III (ATPIII) definition by measuring serum levels of total cholesterol, tryglycerides and glucose. Breakfast size was calculated as: (energy from breakfast/total energy intake) * 2000 kcal. To evaluate the association between breakfast size and MetS prevalence, a multivariable logistic regression model adjusted by potential confounders was used to estimate OR and 95% CI. Results: Prevalence of MetS in our study was 40.7%. The mean breakfast size was 306.6 * 2000 kcal (15% of the total daily energy intake), with 14 (0.4%) participants skipping breakfast. Participants in the highest quartile of breakfast size had a lower MetS prevalence compared to participants in the lowest quartile (ORQ4vsQ1 = 0.62; 95% CI = 0.51–0.76; p-trend < 0.001). No modification of the estimated ORs by sex, breakfast time, and number of eating occasions per day were observed. Conclusion: Our results suggest that higher breakfast size is associated with lower prevalence of MetS in Spanish adults, supporting the importance of a high energy breakfast. Further prospective studies are necessary to confirm these findings.