Novel wastewater treatment plants (WWTPs) are designed to be more energy efficient than conventional plants. One approach to becoming more energy efficient is the pre-concentration of organic carbon through chemically enhanced primary treatment (CEPT) or high-rate activated sludge (HRAS). This study compares these approaches in terms of energy demand, operational costs, organic micropollutants (OMP), and virus removal efficiency. A CEPT pilot-scale plant was operated at a hydraulic retention time (HRT) of 30 min, and a lab-scale HRAS reactor was operated at an HRT of 2 h and a solid retention time (SRT) of 1 d in continuous mode. A minimum dose of 150 mg/L ferric chloride (FeCl3) was required to achieve a threshold chemical oxygen demand (COD)-to-ammonium ratio below 2 g COD to 1 g of NH4+ -N (fulfilling the requirement for a partial nitritation-anammox reactor), reaching high phosphate (PO43-)-removal efficiency (>99%). A slightly lower COD recovery was attained in the HRAS reactor, due to the partial oxidation of the influent COD (15%). The lower PO43- removal efficiency achieved in the HRAS configuration (13%) was enhanced to a comparable value of that achieved in CEPT by the addition of 30 mg/L FeCl3 at the clarifier. The CEPT configuration was less energy-intensive (0.07 vs 0.13 kWh/m3 of wastewater) but had significantly higher operational costs than the HRAS-based configuration (6.0 vs 3.8 c€/m3 of wastewater). For OMPs with kbiol > 10 L/gVSS·d, considerably higher removal efficiencies were achieved in HRAS (80-90%) than in CEPT (4-55%). For the remaining OMPs, the biotransformation efficiencies were generally higher in HRAS than in CEPT but were below 55% in both configurations. Finally, CEPT was less efficient than HRAS for virus removal. HRAS followed by FeCl3 post-treatment appeared to be a more effective alternative than CEPT for COD pre-concentration in novel WWTPs.