Chikungunya virus (CHIKV), an arthritogenic alphavirus, is a significant public health threat in endemic and newly affected regions. This study investigates viral kinetics, immune responses, and the potential of monoclonal antibody (mAb) therapies to mitigate viraemia and transmission during acute CHIKV infection, providing novel insights into early intervention strategies. Using data from 29 patients in Cambodia, serial sampling and viral load quantification revealed that the population-average peak viral load occurred approximately 1.87 days prior to symptom onset. Children demonstrated higher peak viral loads and faster replication rates compared to adults, although symptom severity and burden were similar across age groups. IgM antibodies appeared earlier in adults (median: 4.1 days) than in children (median: 5.1 days; p = 0.036). C-reactive protein (CRP) levels were transiently elevated in about 50% of patients but showed no correlation with disease severity. Mathematical modeling highlighted that prophylactic mAb therapies, when administered three days before symptoms onset, could substantially reduce viral load and potentially prevent detectable viraemia. While these findings underscore the potential of mAbs as an early therapeutic strategy, further studies are necessary to evaluate the robustness of these results and assess their practical implications to curb CHIKV outbreaks by minimizing viraemia and pre-symptomatic transmission.