Background: Multiple immunologic parameters have provided useful prognostic and assessment significance in various cancers, including head-and-neck squamous cell carcinoma (scc). We sought to identify whether pretreatment inflammatory markers could prognosticate recurrence in patients with advanced (stage III or IV) head-and-neck scc who underwent therapy with curative intent in a tertiary care centre between January 2010 and December 2012. Methods: In a chart review, we recorded demographics; primary tumour characteristics; p16 status; pretreatment inflammatory markers, including body mass index (bmi), neutrophil-to-lymphocyte ratio (nlr), C-reactive protein (crp), and serum albumin; therapy received; and date of relapse, death, or last follow-up. The main outcome was relapse-free survival (rfs). Overall survival (os) was a secondary outcome. Results: From among 235 charts reviewed, 118 cases were included: 86 oropharyngeal (50 p16-positive, 18 p16-negative, 17 p16 unavailable, 1 p16 indeterminate), and 32 non-oropharyngeal (7 p16-positive, 19 p16-negative, 6 p16 unavailable). Median follow-up was 2.45 years (25%–75% interquartile range: 1.65–3.3 years). In univariate analysis, p16 status, bmi, modified Glasgow prognostic score, and crp were significant for rfs, but in multivariate analysis, only p16 status, bmi, and crp remained significant. For os, only crp and nlr were significant in both the univariate and multivariate analyses. After adjustment for p16 status, nlr did not remain significant. After adjustment for p16 status, crp remained significant for both rfs and os. Conclusions: In patients with head-and-neck scc, a stronger prognostic value is associated with human papillomavirus status than with nlr and many other factors, including bmi and albumin. However, even though few of our patients had high crp, serum crp remained significant despite p16-positive status.