Objective. To evaluate the diagnostic value of combined detection of color Doppler flow imaging (CDFI) and serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels for neonatal pneumonia. Methods. In this prospective study, 30 newborns with pneumonia and 30 healthy newborns in our hospital from January 2019 to January 2020 were recruited. The healthy newborns were assigned to the control group, and the newborns with pneumonia were assigned to the experimental group. All subjects underwent CDFI and measurement of the levels of serum CRP, PCT, and IL-6. The serum indices and imaging results of the two groups were analyzed, and the specificity and sensitivity of different detection methods in the diagnosis of neonatal pneumonia were calculated and analyzed. Results. The levels of serum CRP, PCT, and IL-6 in the experimental group were significantly higher than those in the control group ( P < 0.001 ). Combined detection had a larger detection area, higher sensitivity, and a superior overall detection outcome than single detection ( P < 0.05 ). The diagnostic results of combined detection and clinical diagnosis in 30 newborns with pneumonia were similar ( P > 0.05 ). Conclusion. The combined detection of CDFI and serum CRP, PCT, and IL-6 levels in the diagnosis of neonatal pneumonia shows a promising diagnostic outcome, so it is worthy of clinical application.