Background and Objectives: hypochloremia is an emerging risk factor for mortality in patients with chronic kidney disease. The pathophysiological mechanisms of this finding are not very clear. Some studies suggest the influence of inflammation as a synergistic factor, so we set out to analyse the association of a novel C-reactive protein-to-serum chloride ratio (CRP/Cl−) with the prognosis of maintenance haemodialysis patients and to assess its relationship with fluid status and body composition measured by bioimpedance. Materials and Methods: the present work is a retrospective cohort study of maintenance haemodialysis patients from our chronic outpatient haemodialysis programme between 1 January 2022 and 31 December 2022. (n = 281). Survival time was collected for all patients and analysed using the Kaplan–Meier method. A Cox proportional hazards regression model was used to evaluate survival probabilities. Variables included in the model were selected using a stepwise selection procedure based on the corrected Akaike information criterion (AICc), which balances model fit and complexity. Results: during a median follow-up of 306 days, 34 patients died. Patients in the fourth quartile of the CRP/Cl− (>0.118 mg/mEq) had higher overall mortality (log-rank test, p = 0.0011). In the Cox multivariate analysis, the variables significantly associated with higher mortality were higher modified Charlson index (MCI), lower body surface area (BSA), lower interdialytic weight gain (IDWG), and higher CRP/Cl− ratio. The latter variable was independently associated with higher overall mortality (adjusted hazard ratio = 1.027; 95% confidence interval [CI], 1.000–1.055 p = 0.0469). Conclusions: Higher CRP/Cl− ratio values were associated with higher all-cause mortality in our maintenance haemodialysis patients.