Ivermectin and doxycycline have been found to be independently effective in killing body lice. In this study, 450 body lice were artificially fed on a Parafilm TM membrane with human blood associated with antibiotics (doxycycline, erythromycin, rifampicin and azithromycin) alone and in combination with ivermectin. Fluorescence in situ hybridisation and spectral deconvolution were performed to evaluate bacterial transcriptional activity following antibiotic intake by the lice. In the first series, a lethal effect of antibiotics on lice was observed compared with the control group at 18 days (log-rank test, P ≤ 10 −3), with a significant difference between groups in the production of nits (P = 0.019, Kruskal–Wallis test). A high lethal effect of ivermectin alone (50 ng/mL) was observed compared with the control group (log-rank test, P ≤ 10 −3). Fluorescence of bacteriocytes in lice treated with 20 ␮g/mL doxycycline was lower than in untreated lice (P < 0.0001, Kruskal–Wallis test). In the second series with antibiotic–ivermectin combinations , a synergistic lethal effect on treated lice (log-rank test, P < 10 −6) was observed compared with the control group at 18 days, associated with a significant decrease in the production of nits (P ≤ 0.001, Kruskal–Wallis test). Additionally, survival of lice in the combination treatment groups compared with ivermectin alone was significant (log-rank test, P = 0.0008). These data demonstrate that the synergistic effect of combinations of antibiotics and ivermectin could be used to achieve complete eradication of lice and to avoid selection of a resistant louse population.