Purpose: Knowledge about oral health-related quality of life (OHRQoL) in adult patients with leukaemia is still limited. Accordingly, aim of this cross-sectional study was to assess OHRQoL and its associations to different parameters in adult patients with newly diagnosed acute leukaemia. Materials and Methods: Participants with first diagnosis of acute leukaemia were consecutively recruited in the Clinic of Hematology and Oncology of the University Medical Center Goettingen. OHRQoL was assessed using the German short form of oral health impact profile (OHIP-G14). Presence of oral initial symptoms, dental health (decayed- [D-T], missing- [M-T] and filled-teeth index [DMF-T]), dental behaviour and periodontal disease severity were assessed. For comparison, a healthy control group (HC) was recruited. Results: Thirty-nine patients with leukaemia and 38 HC were included. In the leukaemia group, a statistically significant and clinically relevant higher OHIP-sum score compared to HC was found (6.13 [3; 0–7] vs 0.87 [0; 0–2], p 0.01). The different subaspects of OHRQoL (patterns) 'oral function' and 'orofacial appearance' were statistically significantly worse in the leukaemia group (p 0.01). Time since diagnosis showed a clinically relevant association to the pattern 'psychosocial impact' (p = 0.06). Patients with oral initial symptoms had a statistically significantly worse OHIP-sum score (p 0.04, V = 0.775). DMF-T (p = 0.03, r = 0.242) and M-T (p = 0.03, r = 0.252) showed an association to OHIP sum score. Moreover, D-T (p = 0.03, r = 0.253) and M-T (p = 0.01, r = 0.296) were associated to orofacial appearance. Additionally, M-T showed an association to pattern 'oral function' (p = 0.01, r = 0.277). Conclusion: Patients with newly diagnosed acute leukaemia show a reduced OHRQoL. This might be particularly caused by oral health situation, especially oral initial symptoms as well as missing teeth.