Aim The purpose of this cross-sectional evaluation was to determine the impact of neuropathic pain (NeP) on patient functioning and Health-Related Quality of Life (HRQoL) under standard care conditions. Methods Patients with NeP or neuropathic and nociceptive pain [Mixed Pain (MP)] enrolled in the DONEGA study, a naturalistic, prospective and multi-centre study of the effectiveness of gabapentin under usual care conditions, were included in this cross-sectional evaluation before starting study treatments. Participants completed the Short Form-McGill Pain Questionnaire, MOS Short Form-12 (SF-12), and Sheehan Disability Scale (ShDS). Multivariate analysis and regression models were used to analyze patient data. Results A total of 1519 patients [mean ± SD; 56.0 ± 13.7 yrs old (58.8% female)] with NeP or MP were enrolled in the study. The mean pain history was 1.1 ± 2.8 yrs, current pain intensity on a 5-point visual analogue scale was 2.8 ± 1.0 and mean pain in previous week was 71.3 ± 19.0 mm. Pain substantially interfered (i.e., score ⩾ 5 on 0–10 scale) with normal work (5.9 ± 3.0), social life (5.7 ± 3.0), and family life (5.3 ± 3.0), producing substantial disability (total ShDS score of 16.9 ± 8.3 pts). Country-standardised physical (PCS) and mental health (MCS) component summary scores of SF-12 indicated significant impairment in both domains compared with the general Spanish population: PCS; −1.13 ± 1.0 SDS (standard deviation score), and MCS; −1.21 ± 0.7 SDS, equivalent to the 15th and 25th percentiles of normative populations, respectively. Conclusions Under standard care conditions, neuropathic and mixed pain are associated with impaired physical and mental QoL, producing a substantial level of disability in these patients.