Main

• Blue (puppeteered by Leslie Carrara-Rudolph in Season 1, then Noel MacNeal in Season 2, and voiced by Victoria Pontecorvo) is the title character and hostess of the show. Blue is a happy-go-lucky female blue dog who is Sprinkles' older sister. She talks and loves to sing, dance, and play with her friends. She often greets others by shouting "Hi, you!" and usually asks viewers open-ended questions. Her catchphrase is "Hoop-dee-doo!"
• Polka Dots (originally puppeteered and voiced by Tim Lagasse in the pilot and shorts, then Peter Linz in Season 1 and Pam Arciero in Season 2) is a sea-foam dog who is Blue's best friend. He creates puzzles for others to solve.
• Frederica "Fred" (puppeteered and voiced by Cheryl Blaylock) is a purple doll who usually pretends that it is her birthday every day. She is one of Blue's good friends.
• Roar "Roary" E. Saurus (puppeteered and voiced by Joey Mazzarino) is a red-orange dinosaur doll who likes to practice roaring.
• Sprinkles (puppeteered and voiced by Joey Mazzarino) is Blue's baby brother and the co-host of the show added to the cast in the second season. Originally a plain white puppy, Sprinkles developed spots upon learning a few things. Sprinkles was created by two sisters, Ashleigh and Lacey Campion through a Nick Jr. competition.
• Doodleboard (originally puppeteered and voiced by Peter Linz in Season 1 & James Godwin in Season 2) is an easel who doodles and draws to tell the viewer to guess what the object is.
• Dress Up Chest (originally puppeteered and voiced by Tim Lagasse in the pilot and shorts, then Tyler Bunch in the series) is a purple treasure chest who gives the others costumes to wear. He occasionally narrates story segments.
• Boogie Woogie (puppeteered and voiced by Joey Mazzarino) is a jukebox who likes to sing and dance.
• Silly Seat (puppeteered by Marc Petrosino & voiced by Jared Goldsmith) is a polka-dotted chair who tells silly jokes, crazy riddles and other funny things.
• Joe (portrayed by Donovan Patton; guest, Season 1; main, Season 2) is a human and Blue and Sprinkles' caretaker who is often seen alongside Sprinkles.

Recurring

• Handy Dandy Journal (voiced by Alex Hoffman) is an animated talking notebook whose face and design resembles that of Polka Dots. Blue writes and draws various thoughts about specific aspects of episodes in his pages.
• Dictionary (voiced by Brianna Gentilella) is a yellow animated book containing many words and their meanings and definitions that Blue looks in almost every day to find out what the Word of the Day is. She has a face and has the ability to speak, similar to all other residents of Blue's Room.
• Key (voiced by Jared Goldsmith) is an animated magical key Polka Dots keeps in his pocket. He opens Dress Up Chest's lock and is colored gold and orange.
• Moona (voiced by Christiana Anbri) is an animated green and blue-colored fairy made of crescent shapes who tells Blue it is time to go home and appears at the end of each segment and episode.
• Antonio (portrayed by Antonio Ortiz) is a young boy who sometimes visits Blue and her friends at the playroom.
• Grandma Roary (puppeteered and voiced by Heather Asch) is the elderly grandmother of Roary.
• Cookbook (voiced by Victoria Pontecorvo) is an animated red and white book full of food recipes.
• ABC Puppy (puppeteered by Matt Vogel and voiced by Jared Goldsmith) is a pink puppy who lives in Alphabet City and loves letters.
• Colors Puppy (puppeteered by Noel MacNeal and voiced by Jared Goldsmith) is an orange puppy who lives in Color Town and loves colors.
• Princess of Numbers Puppy (puppeteered by Lisa Buckley and voiced by Christiana Anbri) is a purple puppy who lives in Numbers Kingdom and loves numbers.
• Shapes Puppy (puppeteered by Pam Arciero and voiced by Lance Chantiles-Wertz) is a yellow puppy who lives in Shapes Forest and loves shapes.

Series overview

Season 1 (2004–2005)

Season 2 (2006–2007)

Episodes on Nick Jr. compilation DVDs