Chills and vomiting have traditionally been associated with severe bacterial infections and bacteremia. However, few modern studies have in a prospective way evaluated the association of these signs with bacteremia, which is the aim of this prospective, multicenter study. Patients presenting to the emergency department with at least one affected vital sign (increased respiratory rate, increased heart rate, altered mental status, decreased blood pressure or decreased oxygen saturation) were included. A total of 479 patients were prospectively enrolled. Blood cultures were obtained from 197 patients. Of the 32 patients with a positive blood culture 11 patients (34%) had experienced shaking chills compared with 23 (14%) of the 165 patients with a negative blood culture, P = 0.009. A logistic regression was fitted to show the estimated odds ratio (OR) for a positive blood culture according to shaking chills. In a univariate model shaking chills had an OR of 3.23 (95% CI 1.35–7.52) and in a multivariate model the OR was 5.9 (95% CI 2.05–17.17) for those without prior antibiotics adjusted for age, sex, and prior antibiotics. The presence of vomiting was also addressed, but neither a univariate nor a multivariate logistic regression showed any association between vomiting and bacteremia. In conclusion, among patients at the emergency department with at least one affected vital sign, shaking chills but not vomiting were associated with bacteremia.