Lyme borreliosis (LB) is a naturally occurring transmissible disease caused by Borrelia burgdorferi sensu lato. Some patients develop LB after effective treatment of the acute stage of the disease with antibiotics, which may suggest involvement of chemokines and cytokines in its pathogenesis. This study aimed to assess serum levels of chemokine (C–C motif) ligand 19 (CCL19) and interleukin-23 (IL-23) in patients with post-Lyme syndrome (PLS) and neurological involvement, and to examine their association with clinical manifestations and laboratory parameters. We examined 70 individuals (26 [37.1%] male and 44 [62.9%] female) with confirmed LB who presented with neurological symptoms persisting or recurring within 6 months following the recommended antibiotic treatment. The serum levels of CCL19 and IL-23 were determined using a solid-phase enzyme immunoassay; CCL19 was high in 12 (17.1%) participants, and IL-23 in 10 (14.3%). Significant positive correlations were established between the concentrations of CCL19 and IL-23 (r = 0.65, p < 0.0001) and their hyperproduction (r = 0.79, p < 0.0001). The likelihood of developing Lyme disease after treatment increased significantly in association with overproduction of CCL19 and, especially, IL-23: odds ratio — 5.00; 95% CI: 1.00–24.84, p = 0.04, and 22.42; 95% CI: 1.25–399.93, p = 0.03, respectively. No correlation was found between the concentration of CCL19, IL-23, and the levels CRP, IgM and IgG antibodies to B. burgdorferi, ass well as IgG antibodies to SARS-CoV-2. A subject matter being discussed in the paper is how CCL19, IL-23 and other mechanisms participate in post-treatment pathogenesis of Lyme disease with neurological damage.