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In this retrospective cohort study of patients with tick-borne encephalitis (TBE), the clinical outcome in relation to co-infection with B. burgdorferi sensu lato (s.l.) and, specifically, the effect of antibiotic treatment on clinical outcome in patients with TBE who were seropositive for borreliae but who did not fulfil clinical or microbiologic criteria for proven co-infection, were assessed at a single university medical center in Slovenia, a country where TBE and Lyme borreliosis are endemic with high incidence. Among 684 patients enrolled during a seven-year period from 2007 through 2013, 382 (55.8%) had TBE alone, 62 (9.1%) had proven co-infection with borreliae and 240 (35.1%) had possible co-infection. The severity of acute illness was similar in all the groups. The odds for incomplete recovery decreased during a 12-month follow-up but were higher in women, older patients, and in those with more severe acute illness. Incomplete recovery was not associated with either proven (odds ratio (OR) 1.21, 95% confidence interval (CI) 0.49–2.95 p = 0.670) or possible co-infection (OR 0.95, 95% CI 0.55–1.65 p = 0.853). Among patients with possible co-infection, older patients were more likely to be prescribed antibiotics, but the odds for incomplete recovery were similar in those who received antibiotics and those who did not (OR 0.82, 95% CI 0.36–1.87 p = 0.630), suggesting that routine antibiotic treatment in patients with TBE and possible co-infection may not be warranted.