Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region. The severity of infection ranges from mild features to multiorgan failure and death. The aim of this prospective study was to define the O. tsutsugamushi loads in the blood samples of patients with scrub typhus on the day of hospital admission and to determine whether this was associated with disease severity. Quantitation was performed using a real-time PCR assay targeting the 16S rRNA gene of O. tsutsugamushi. A total of 155 patients with a confirmed diagnosis of scrub typhus had a median (interquartile range [IQR], range) O. tsutsugamushi DNA load in blood of 13 (0 to 334, 0 to 310,253) copies/ml. This included 74 patients who had undetectable bacterial loads. An analysis of bacterial load versus clinical features for all 155 patents demonstrated that duration of illness (P < 0.001), presence of eschar (P = 0.004), and concentrations of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (P < 0.001 for all three) were positively correlated with bacterial load. Patients who died had a significantly higher bacterial load than those who survived (mean [standard deviation] values: 17,154 [12.7] versus 281 [5.2] copies/ml; P < 0.001). This study has demonstrated a relationship between bacterial load and disease severity in adults with scrub typhus.