Objectives The aim of this study was to evaluate the optimal energy level of virtual monoenergetic images (VMIs) from photon-counting detector computed tomography (CT) for the detection of liver lesions as a function of phantom size and radiation dose. Materials and Methods An anthropomorphic abdominal phantom with liver parenchyma and lesions was imaged on a dual-source photon-counting detector CT at 120 kVp. Five hypoattenuating lesions with a lesion-to-background contrast difference of −30 HU and −45 HU and 3 hyperattenuating lesions with +30 HU and +90 HU were used. The lesion diameter was 5–10 mm. Rings of fat-equivalent material were added to emulate medium- or large-sized patients. The medium size was imaged at a volume CT dose index of 5, 2.5, and 1.25 mGy and the large size at 5 and 2.5 mGy, respectively. Each setup was imaged 10 times. For each setup, VMIs from 40 to 80 keV at 5 keV increments were reconstructed with quantum iterative reconstruction at a strength level of 4 (QIR-4). Lesion detectability was measured as area under the receiver operating curve (AUC) using a channelized Hotelling model observer with 10 dense differences of Gaussian channels. Results Overall, highest detectability was found at 65 and 70 keV for both hypoattenuating and hyperattenuating lesions in the medium and large phantom independent of radiation dose (AUC range, 0.91–1.0 for the medium and 0.94–0.99 for the large phantom, respectively). The lowest detectability was found at 40 keV irrespective of the radiation dose and phantom size (AUC range, 0.78–0.99). A more pronounced reduction in detectability was apparent at 40–50 keV as compared with 65–75 keV when radiation dose was decreased. At equal radiation dose, detection as a function of VMI energy differed stronger for the large size as compared with the medium-sized phantom (12% vs 6%). Conclusions Detectability of hypoattenuating and hyperattenuating liver lesions differed between VMI energies for different phantom sizes and radiation doses. Virtual monoenergetic images at 65 and 70 keV yielded highest detectability independent of phantom size and radiation dose.