OBJECTIVE To define optimal keV settings for advanced monoenergetic (Mono+) dual-energy computed tomography (DECT) in patients with head and neck squamous cell carcinoma (SCC). METHODS DECT data of 44 patients (34 men, mean age 55.5 ± 16.0 years) with histopathologically confirmed SCC were reconstructed as 40, 55, 70 keV Mono + and M_0.3 (30 % 80 kV) linearly blended series. Attenuation of tumour, sternocleidomastoid muscle, internal jugular vein, submandibular gland, and noise were measured. Three radiologists with >3 years of experience subjectively assessed image quality, lesion delineation, image sharpness, and noise. RESULTS The highest lesion attenuation was shown for 40 keV series (248.1 ± 94.1 HU), followed by 55 keV (150.2 ± 55.5 HU; P = 0.001). Contrast-to-noise ratio (CNR) at 40 keV (19.09 ± 13.84) was significantly superior to all other reconstructions (55 keV, 10.25 ± 9.11; 70 keV, 7.68 ± 6.31; M_0.3, 5.49 ± 3.28; all P < 0.005). Subjective image quality was highest for 55 keV images (4.53; κ = 0.38, P = 0.003), followed by 40 keV (4.14; κ = 0.43, P < 0.001) and 70 keV reconstructions (4.06; κ = 0.32, P = 0.005), all superior (P < 0.004) to linear blending M_0.3 (3.81; κ = 0.280, P = 0.056). CONCLUSIONS Mono + DECT at low keV levels significantly improves CNR and subjective image quality in patients with head and neck SCC, as tumour CNR peaks at 40 keV, and 55 keV images are preferred by observers. CONCLUSIONS • Mono + DECT combines increased contrast with reduced image noise, unlike linearly blended images. • Mono + DECT imaging allows for superior CNR and subjective image quality. • Head and neck tumour contrast-to-noise ratio peaks at 40 keV. • 55 keV images are preferred over all other series by observers.