Fewer than half the patients with health conditions such as asthma, diabetes and heart complaints had a flu jab last year.
Figures released by health managers also show that just over a quarter of pregnant women had the injection, despite being considered "at risk" if they catch the infection.
Dr Tim Davies, deputy director of public health for Leicester, Leicestershire and Rutland, said: "People with health conditions are used to managing their health.
"However, many do not realise the risk that flu can pose.
"Getting flu when you already have a health condition can lead to serious complications and can even be a killer."
Figures show that in Leicestershire and Rutland, 48.4 per cent of people with health conditions and 29.3 per cent of pregnant women had a flu jab last winter.
In the city, 49.8 per cent of people with health conditions and 26 per cent of women were vaccinated.
Dr Davies said: "The flu vaccine changes every year to fight the latest strains of flu, so even if you had a jab last winter you need another one this year to stay flu safe.
"The flu jab is completely safe and doesn't carry the live flu virus, so it can't give you flu."
Each winter, East Midlands Ambulance Service sees an increase in the number of emergency calls received and many are from people suffering from flu.
Louise De Groot, clinical quality manager and emergency care practitioner for East Midlands Ambulance Service, said: "Often people suffering from flu with a long-term condition will need transporting into hospital for treatment.
"Not only is that upsetting for themselves and their loved ones, but it's also impossible for them to work or look after their kids when they're being treated in hospital.''