This study aimed to demonstrate that severe neurological motor deficits in the context of late tick-borne disease with mixed microorganism involvement are eligible for long-term combined antibiotic/antiparasitic treatments. The inclusion criteria were: 1. neurological limb paralysis with a disability score >4 according to the EDSS Kurtzke disability scale; 2. serological tests pointing to an involvement of the main tick-borne microorganismsBorrelia burgdorferis.l.,Babesia,Anaplasma, andBartonella; 3. a general disease for more than 6 months with fatigue, pain and subjective cognitive deficit. The patients were administered long-term treatments with repeated cycles (at least three) of 35-day IV ceftriaxone and repeated oral regimens of azithromycin–doxycycline and azithromycin–doxycycline–rifampicin. ForBabesia, repeated courses of atovaquone–azithromycin were administered. Ten patients had intractable or severe motor deficits before treatment in the context ofBorrelia(two cases)Borrelia–Babesia(four cases),Borrelia–Babesia–Anaplasma(two cases),Borrelia–Babesia–Anaplasma–Bartonella(one case) andBabesia–Anaplasma(one case). For several months, five had been in wheelchairs, and four had been walking with sticks. Seven patients out of 10 (70%) showed complete remission after a mean active treatment duration of 20.1 + 6.6 months, with a mean number of 4 ceftriaxone cycles. Three patients showed an initial remission but suffered secondary antibiotic/antiparasitic-resistant motor recurrences. Among the nine patients withBorreliaserologic positivity, treatments obtained complete remission in seven cases (77%). The findings of this ten-case series suggest the usefulness of long-term antibiotic/antiparasitic treatments in patients with severe late tick-borne neurological deficits with highly significant elements of tick-borne involvement.